As the world narrowed its focus to the pandemic this past year, the McGovern Medical School scientific community likewise quickly switched its research attention, collaborating and innovating to discover new therapies and treatment options for COVID-19 patients.
In March 2021, Holger Eltzschig, MD, PhD, and his research team started molecular and translational research experiments using the COVID-19 virus, SARS-CoV2, to find novel approaches to help patients affected by acute respiratory distress syndrome (ARDS) – a severe complication of COVID-19 that can lead to death.
“Close to 95 percent of those who die from COVID, are dying from ARDS. The lungs are inflamed and if steroids or ECMO don’t work, right now that is all we have to offer these patients,” explained Eltzschig, professor and chair of the Department of Anesthesiology.
In vivo research with the highly contagious SARS-CoV2 virus requires a specialized BSL-3 laboratory – defined by the Centers for Disease Control and Prevention as a lab that works with microbes either indigenous or exotic that may cause “serious or potentially lethal disease through respiratory transmission.”
“We started in April 2020 to get the BSL-3 up and running with biosafety and animal protocols – and from the idea to actually doing molecular and translational research took us almost a year,” said Eltzschig, John P. and Kathrine G. McGovern Chair and associate vice president for Translational Research and Perioperative Programs.
Fortunately, an existing BSL-3, in use for tuberculosis research by Jeffrey Actor, PhD, professor of pathology and laboratory medicine, was available in the Medical School Building and helped to expedite the buildout for the COVID-19 research.
“To build one from scratch would require new floors and ceilings, a new HVAC system, a new autoclave, animal housing – it would have taken a long time. We were lucky that Dr. Actor had an existing BSL-3 and was able to dovetail as a collaborator to be able to fast track this while keeping proper safety in place,” explained Brett Haltiwanger, PhD, safety manager of the Biological Safety Program.
The pandemic forged new research opportunities between the departments of pathology and anesthesiology.
“When the pandemic hit, a number of individuals approached us, and our department formed a committee to evaluate which opportunities would be most appropriate to share not just short term but long-term collaboration to meet the needs of the facility and translational benefit for disease pathology,” Actor explained. “Dr. Eltzschig’s lab fit that beautifully – he also had everything in place to ramp up his investigations in a time period that was doable so we could proceed along a path to get productive research done.”
The BSL-3 designation requires an annual validation of the facility from the university’s Biological Safety Program as well as biosafety training, BSL-3 training, PPE training and respirator fit test, and certification of personnel to handle infectious reagents. The lab also must have approval from the university’s Institutional Biosafety Committee to work with patient samples and the SARS-CoV2 virus. The native SARS-CoV2 human viruses are supplied directly from the NIH, National Institute of Allergy and Infectious Diseases.
“We developed lab-specific standard operating procedures, and the BSL-3 has two biosafety cabinets so we are able to designate one for tuberculosis research and one for SARS-CoV2 virus research,” Haltiwanger explained, adding that a new pass-through autoclave was also installed.
“So far, I’ve shifted my work to the COVID vaccine – examining how to push the immune system to alleviate disease pathology following vaccination. I just received word of funding to continue this work, and it aligns perfectly with the work that the Eltzschig lab is doing,” Actor said. “We have an understanding in place for flexible research on pathogens in the BSL-3, based on priority.”
As the BSL-3 lab was readied for COVID research, a BSL-2-enhanced lab was outfitted for the Eltzschig group to accommodate their work with biospecimens from a clinical trial involving COVID-19 patients.
“We got them up and running in the BSL-2-enhanced lab first, which is a BSL-2 lab that follows BSL-3 lab protocols,” Haltiwanger explained.
Everyone working in the labs must be trained to the specific criteria. Researchers work in pairs – using a buddy system and follow tightly choreographed instructions.
“Things have been going smoothly with the institution’s help,” said Xiaoyi Yuan, PhD, assistant professor of anesthesiology. “We have an isolated room to analyze biospecimens and are expanding to higher capacity. We are looking at advance biomarkers and measure target gene samples.”
A variety of ARDS samples with and without COVID and different strains of the virus allow for innovative research.
“We do experiments to affect the alveolar epithelial cells to understand the conditions where the virus propagated. We also infect mice to study host response against viral infection,” said Yanyu Wang, PhD, Eltzschig lab manager.
“We understand the biological pathways and are really excited about this opportunity,” Eltzschig added. “We hope this one year of buildup will allow us to do transformative research that integrates the biology of the virus and the response of the human lungs. We feel privileged to be in this position.”
In addition to collaborative support from Jaiyeola Thomas-Ogunniyi, MBBS, interim chair of the Department of Pathology, the group received institutional support with vaccination priority.
“We are thankful to the institution – especially Dr. Blackburn, Dr. Colasurdo, to create the infrastructure important for this long-term research. It was also incredibly generous of Dr. Actor to give us access to his lab, and it has been outstanding to work with him,” Eltzschig said.
As the group continues its work, safety is always paramount.
“I’m on speed dial with them. It’s important to have that level of communication in a safety environment,” Haltiwanger said, adding that Environmental Health and Safety performs monthly surveys of the BSL-3 environments.
And COVID-19 research isn’t a flash in the pan, according to Eltzschig.
“We will be studying COVID-19 and using this BSL-3 for the next 5-10 years. We need to be very prepared to treat and prevent viral pneumonia and must understand the biology of the disease and learn to think out of the box,” Eltzschig said.