By Yash Pershad
Stanford researchers across disciplines and departments have launched research projects to tackle the COVID-19 pandemic and its effects on daily life with a wide range of approaches.
Scientists, physicians and engineers are collaborating to find drugs and vaccines for the disease, combat personal protective equipment (PPE) and ventilator shortages, test existing therapeutics in nationwide clinical trials and optimize the productivity of the work-from-home workforce.
Here, we highlight a few of many Stanford research projects.
Searching for therapeutics
Research to find treatments for COVID-19 has focused on discovering antibodies to enable peoples’ immune systems to fend off the virus that causes COVID-19, known as SARS-CoV-2, and finding drugs that target viral proteins or human cells that help the virus spread.
Toward the first aim, in late January, genetics M.D./Ph.D. student Binbin Chen and his colleagues started a project to identify fragments of SARS-CoV-2 that can be used for COVID-19 vaccines.
“Vaccines are one of the most powerful tools to curb a pandemic and prevent its recurrence,” Chen said. “However, vaccine design is often a guessing game with new pathogens … so artificial intelligence tools built upon immunology knowledge and data can provide a better educated guess … and increase the chances of finding an effective vaccine.”
Chen and his co-authors have made a list of vaccine candidates available in a bioRxiv preprint in an effort to help bring vaccines to the clinic. They are also organizing a long-term project to collect patient samples for future pandemics.
In the midst of the pandemic, Chen found many willing and readily accessible collaborators. Some of those volunteering to help out were from across the globe. A senior author of one of the first SARS-CoV-2 protein structure papers from China replied to Chen’s email within four hours. And, in addition to international help, Chen found assistance much closer to home.
“I also live with one on my academic collaborators — my husband — so we get a lot done!” Chen said.
Stefano Rensi Ph.D. ’18, a research engineer in the bioengineering department, has taken a different approach to the problem of finding therapeutics: Repurpose existing drugs with the goal of getting them to the front lines as soon as possible.
Rensi and colleagues including bioengineering professor Russ Altman Ph.D. ’89 M.D. ’90 predicted that existing compounds can bind and inhibit a key protein — transmembrane protease, serine 2 (TMPRSS2) — that facilitates viral invasion of human cells.
Feeling a sense of urgency, Rensi has put other projects on hold to help out with the crisis. He believes others in the Stanford community and around the world have done the same.
“People across institutions and industry are all … sharing information, ideas and results,” Rensi said. I can’t think of any better use of our time or training than fighting a global pandemic.”
As computational researchers, Rensi and his co-authors now collaborate with others to test their predicted compounds in experimental assays, or tests, to see if their drugs can inhibit the key enzyme required for the virus to enter and infect human cells.
“If [the assays] pan out, we will advance to animal testing and then clinical trials,” Rensi said.
Starting rapid, adaptive clinical trials
Others, including Kari Nadeau, professor of medicine and pediatrics, and Neera Ahuja, clinical professor of medicine, have worked to bring clinical trials sponsored by the National Institutes of Health (NIH) to Stanford.
Nadeau and Ahuja are spearheading a trial at Stanford that is also being conducted at 64 other sites globally to test the safety and efficacy of remdesivir in hospitalized adult patients diagnosed with COVID-19. Remdesivir is a novel antiviral drug originally developed as a treatment for Ebola; it mimics a building block of viral genetic material and works to prevent viral replication.
The goal of the collaboration between Nadeau, Ahuja and the NIH is to quickly make more treatment options available for COVID-19 patients.
“In very rapid form, we were able to get the trial up, site-approved and open for enrollment in about a week, which is really unheard of,” Ahuja said.
Nadeau was excited to be able to work with the NIH and expressed gratitude for physicians like Ahuja, who are balancing patient care with the coordination of new clinical trials to obtain much-needed data on therapies for COVID-19.
“Because there is no current therapy, we should be compelled to be a part of the best clinical trials out there,” Nadeau said.
Nadeau also pointed out that clinical trials must be designed to anticipate the potential genetic mutations of SARS-CoV-2, as viruses can gain resistance to single therapies, often necessitating combinations of multiple drugs.
“There are methodologies in statistics and trial design — adaptive trial design — where you can combine more than one drug at a time,” Nadeau said. “Viruses are super smart and can develop resistance. So, we are going to start an adaptive trial design for combination therapies.”
Coping with working from home
Researchers like Pablo Paredes, a radiology and psychiatry and behavioral services instructor, are working on solutions to alleviate the added stress for many people who are now being asked to work from home while balancing family life.
Paredes and his collaborators are developing web-based tools — specifically a Google Chrome extension and mobile app — to support healthy routines for productivity, reduce over-consumption of stressful media and web content, and encourage work-life balance and family interaction.
The project, called “Home Sweet Office” (HSO), integrates mental health and stress management interventions created in Paredes’s lab, the Pervasive Wellbeing Technology Lab, with a former project from the lab of Michael Bernstein, associate professor of computer science.
“We believe the new normal of human-human interaction will demand new ways of thinking and new tools for productivity, stress and mental health,” Paredes said.
HSO aims not only to create tools to increase mental health and stress management, but also aggregate critical data for the future.
“The data generated… will serve towards studying the longitudinal causal relationships between stress, productivity, and mental health,” Paredes said.