Amid COVID-19 Pandemic, How Is Biotech Responding?

In light of the COVID-19 pandemic, virtually every facet of life is altering daily. This is true of industry as well. In biotechnology, specifically, the effects of COVID-19 are both immediate, and potentially long-lasting. Thankfully, biotech has the ability to make a meaningful impact in the current public health crisis. To explore this more, we sat down with Natalie Ma, Ph.D., synthetic biologist and a Blavatnik Fellow at Yale's Office of Cooperative Research.

OCR: Many industries are halting efforts currently due to the COVID-19 coronavirus. How has it immediately impacted the biotechnology industry?

Natalie Ma: It has immediately impacted the biotechnology industry in two ways: reshuffling resources to combat the COVID-19 pandemic and either delaying or re-evaluating timelines for all other projects. In terms of the first, we’ve seen a lot of diagnostics companies shifting focus to develop tests for SARS-CoV-2, the coronavirus that causes COVID-19 (in-progress tracking document). Similarly, we have seen medical device and materials companies kicking into high gear to tackle the shortage of personal protective equipment and ventilators. This has resulted in the development of diagnostic tests and medical equipment that have been greenlighted by the FDA for emergency use authorization. I think the big challenge is now that these have authorization for use (which is separate from a full FDA approval), how do we scale production of these things and get them to where they are needed? With supply chain disruptions across the globe, this has been challenging.

In terms of disruption to biotech projects, everything from the supply chain disruption to work-from-home orders to strain on the hospital systems will mean delays in therapeutic and medtech development. As STAT highlights, biotechs are having to decide which projects are mission-critical. Because supply chains for raw materials and tools have taken a hit and many labs have either redirected to COVID-19 projects or suspended work to protect the health of their employees, this will delay pre-clinical research and development. In addition, conducting clinical trials for FDA approval is incredibly difficult—you’re asking overwhelmed hospitals to focus on an additional thing and asking patients, many who have underlying medical conditions that put them at risk of complications or death from the virus, to come into hospitals for treatment. In the longer term, we’ll likely see the delays in the approval of new drugs across the board because every step in the drug development process will be impacted.

OCR: What types of research are changing direction to aid COVID-19 research? Can you provide an example(s) at Yale?

NM: With this urgent need, everyone is pushing to develop ways to combat COVID-19. At Yale, specifically:

• Anna Pyle is working to provide a novel reverse transcriptase called Marathon RT, which may be useful for understanding COVID-19, directly into the hands of researchers.
• At the grassroots level, you also have labs self-organizing to meet the gap in diagnostic testing by running tests in the lab (e.g., UW Seattle has released its method for anyone to use).
• Kleo Pharmaceuticals, Inc., a Yale spinout, has entered into a research collaboration with South Korea -based Green Cross LabCell (GCLC), a pioneer in the next generation of allogeneic, or “off-the-shelf” natural killer (NK) cell therapies, to rapidly advance testing of both advanced technology platforms in combination as a potential therapy for COVID-19 patients.
• There is a project to use an existing vaccine platform that has been successfully used to create a vaccine for Ebola virus to develop a vaccine for COVID-19, to repurpose antivirals that are approved or in development.
• We are also working on initiating a trial for a treatment for Acute Respiratory Distress Syndrome (the major complication of COVID-19) that may make the infection less severe, so that fewer people develop severe complications and need ventilators. This could help patients a lot and alleviate significant strain on the health care system.
• There are also efforts to create solutions to the ventilator shortage by critical care physicians at Yale.

OCR: How could this impact clinical trials already taking place? Can they start and stop? Can you provide an example?

NM: This considerably depends on the current status of the trial. There are some biotechs that have gotten enough data that they can finish up the trial without too much difficulty, which is probably one of the best-case scenarios in this situation. As for trials that haven’t yet started (with the exception of those for COVID-19), the most responsible thing to do from a medical standpoint is to delay them to minimize risk to both health care staff and patients. We’ve seen large pharma such as Eli Lilly slashing clinical trials, and a biotech I’m working with is holding off on opening a trial here at Yale as well. Others are moving to digital clinical trials so patients don’t need to come to clinic and hospital sites. However, because digital clinical trials are so nascent and there are many things only health care staff can do (such as blood draws), the number of trials that can go digital is limited.

I think those with clinical trials currently in progress face the toughest challenges. Clinical Research IO recently reported that 24% of physicians leading trials have stopped enrolling patients in trials, and those who haven’t are considering doing so. But biotech companies have to pay to keep trial sites open, meaning that they are running up costs even when they cannot treat patients and collect data on whether their therapy works. At the same time, closing down and re-opening trials will also be incredibly costly. So they are stuck between a rock and a hard place, unless they can strike deals for reduced costs to do either of those.

OCR: What type of research do you anticipate will be affected most?

NM: As I mentioned above, this will impact nearly all research—that’s across academia, biotech startups, the pharma industry, contract research organizations, government labs. There’s just so much experimental work that still relies on research labs. Had this struck 10-20 years from now, there may have been enough cloud-based lab automation that would have enabled research to continue, but not now. The only group that may escape is computational research, but even that may rely on supercomputers housed on campus that are in power-saving mode or not being maintained. On a lighter note, I suspect there will be a deluge in grant and manuscript submissions, as that is something labs can continue even without lab access. And hopefully they will all be impeccably written and formatted.

OCR: Do you think biotech researchers could be doing more? What is Yale doing?

NM: That’s a hard question. There are already so many researchers risking their health and giving their time to continue conducting research on COVID-19. But there are a lot of us who are not actively working on this and want to—I know there are folks in my Ph.D. lab group looking for ways to contribute, and a researcher at the Broad Institute created a Scientist Volunteer form for scientists interested in helping out to register. The challenge isn’t in getting people to help, but in organizing them and providing operational guidance. Physicians have Doctors without Borders and engineers have Engineers Without Borders, but I don’t know of an equivalent organization for lab researchers. And because this is an issue we haven’t faced frequently; I think few people have thought about how to best organize and plug researchers into combating the pandemic. So the ability of researchers to contribute depends on there being a highly invested individual in a position of power (such as a faculty member or center director, as we see at UW Seattle) to help organize and get researchers involved.

OCR: Who are trusted voices?

NM: Where to get true and valid information is a big concern on everyone’s minds. While this isn’t a comprehensive list, I would put a lot of trust in the following:

• The Johns Hopkins Center of Health Security (@JHSPH_CHS), and in that group particularly Tom Inglesby—the CSH has been thinking about pandemic threats for a long time and actually ran a tabletop pandemic exercise late last year to better understand how the world would respond to a pandemic.
• In terms of individuals, I would say Akiko Iwasaki (@VirusesImmunity) and Vincent Racaniello (@profvrr). Former FDA Commissioner Scott Gottlieb (@ScottGottliebMD) has also been a leading voice in sharing information of what we are, can, and should be doing.
• Nongovernmental organizations such as the World Health Organization (@WHO), the Infectious Disease Society of America (@IDSAInfo), the European Society for Microbiology and Infectious Diseases (@ESCMID)

And note while I would trust these voices, that does not make them infallible. But I do think the information that they are sharing is critically thought through and more likely to be correct.

OCR: What could people be doing to combat the pandemic if they aren’t health care workers and researchers?

NM: Many people want to help combat the pandemic but may not be health care workers and researchers. And when people feel like they cannot do anything to help, it can lead to fear, anxiety, and negative health effects.

Besides observing social distancing (meeting with as few people as possible, outside of those they already live with), proper handwashing, and minimizing travel and working from home as much as possible, one of the things anyone can do is learn more about the COVID-19 and the pandemic! For example, there are courses free and available to everyone on COVID-19:

• COVID-19 Course from the London School of Hygiene and Tropical Medicine
• COVID-19 Course from Johns Hopkins Bloomberg School of Public Health
• WHO trainings that support pandemic preparedness (although geared more towards health care professionals and leaders).

You could also take the chance to learn more molecular biology, virology, and epidemiology to better understand the pandemic:

• Coursera Molecular Biology Course
• KhanAcademy Molecular Biology Course
• Free Virology Class Resources

The other (very) important thing everyone can do is remember to thank the essential workers that are still working during the pandemic.