Lukas Flippo

Although the outbreak of COVID-19 has caused the suspension of many of Yale’s “non-critical” labs, University researchers are continuing to dedicate themselves to understanding and fighting the virus.

University Provost Scott Strobel put a pause on all non-critical laboratory work by March 17 in an effort to reduce the rapid spread of coronavirus. The mandate, which was directed at any lab not directly involved with studying the disease and critical maintenance, has shut down lab work across Yale, encouraging researchers to continue working on projects from home that do not require laboratory instruments.

In May, Yale announced three phases of research reactivation on campus. On June 1, a limited number of faculty and staff were brought back. Phase two began on July 20; the university expects to enter phase three on August 24.

“It is an extraordinary circumstance, unprecedented in human history,” said Richard Bucala ’79 GRD ’79, Chief of Rheumatology, Allergy & Immunology and Rheumatologist in Chief at Yale New Haven Health. “There’s nothing more important than human health. We all work very hard. We’re all very professional, but this dedication should never jeopardize your health or the health of your family.”

These restrictions also spell out additional training for researchers that are staying in the labs. With biocontainment and social distancing, scientists must find new ways to adapt and continue their work. In addition, because researchers did not account for the virus in their budgets and do not have access to grants to fund these projects, the coronavirus research can only be funded by institutional and personal funds, said Naftali Kaminskie, the School of Medicine’s Chief of Pulmonary, Critical Care and Sleep Medicine.

Despite the necessity of these measures, the suspension of lab research may jeopardize years of work and experimental progress, including studies done in Professor Michael Nitabach’s lab at the Yale School of Medicine. His lab has little to do with COVID-19 research, as his group studies the basic biology of neural circuitry. In line with the University’s mandate, Nitabach wrote that he has terminated all “ongoing experimental plans” except the maintenance and preservation of key worm and fly strains, specimens that would be “very time-consuming and difficult to recreate in the future.”

Lukas Flippo

The labs that have remained open, however, are working hard to investigate the source, spread and treatment of coronavirus. Many researchers are putting aside their own work to focus exclusively on the outbreak, lending their expertise to add to the growing base of scientific research about the risks of the virus and to dispel misinformation. According to Saad Omer, director of the Yale Institute for Global Health, the best policy surrounding COVID-19 is found at the intersection of strong scientific information and a clear plan of action.

The Connecticut Emerging Infections Program — a collaboration between the Connecticut Department of Public Health, the Centers for Disease Control and Yale — tracks confirmed coronavirus cases to identify people at risk of contracting the virus. Using this data, scientists are able to chart an accurate picture of who is getting sick in order to develop targeted prevention strategies for groups with an increased risk of infection.

In a further attempt to accurately identify the number of cases, Yale scientists are looking for more cost-effective and efficient ways to test for the disease. On April 22, a preprint was released for a study that suggested saliva might be the sought-after solution for testing. The preprint — a study draft that has not yet undergone peer review — documented the research from six weeks of working with saliva samples from healthcare workers and 44 inpatients at Yale New Haven Health. 

The study involved side-by-side comparisons between saliva samples and clinician-administered nasopharyngeal swabs, which is the current preferred method of testing for the virus. The study reported that “using saliva for SARS-CoV-2 detection is more sensitive and consistent than using nasopharyngeal swabs.”

If the study proves consistent in larger sample sizes, this could be a significant discovery. Nasopharyngeal tests have been proven to be unreliable, yielding contradictory results over time.

“Saliva is a more consistent and easier test to take and always lower risk, and it saves time and PPE,” said Anne Wyllie, associate research scientist in epidemiology and lead author on the paper. “It could be really transformative for our testing efforts at the moment in a healthcare setting.”

Testing with saliva would solve many issues faced by healthcare workers today, including the current testing capacity, as saliva tests could be done at home by spitting into a cup and dropping it off at a testing facility. Testing at home would also minimize the risks for healthcare workers, who would not need to have physical contact with patients in order to test them.

However, the transition to saliva testing is not without its challenges. Many labs are still not certified to use saliva samples, and the study requires more data to confirm Wyllie’s findings. In the meantime, Wyllie and her team are continuing to generate new data to make an even more convincing case.

Lukas Flippo

Other labs on campus are working on finding a treatment for the disease. The Yale Chemical and Biophysical Instrumentation Center (CBIC) is investigating a treatment for acute respiratory distress syndrome (ARDS), a prominent symptom of COVID-19.

Currently, the CBIC is working with New England Discovery Partners, a contract research organization specializing in drug discovery, who has already synthesized a 10-gram anti-inflammatory treatment.

“The active ingredient is a very challenging, light-sensitive molecule,” said Michael Van Zandt, the CEO of New England Discovery Partners. In order to commercialize the drug, the team has to significantly increase its production. New England Discovery Partners is using the CBIC’s nuclear magnetic resonance spectroscopy machine to verify the efficacy of their efforts in increasing the yield of the molecule.

The Yale Center for Engineering Innovation and Design (CEID), another core facility, is also lending its technologies and resources, including its 3D printer. Scientists are doing projects exploring the printer’s ability to address the shortage of personal protective equipment.

Other scientists are looking towards antibody research to help understand questions about immunity. Although much of the work is still theoretical, the investigation could lead to breakthroughs in treatment and the development of vaccines. Aaron Ring is an assistant professor of immunobiology whose lab is studying SARS-CoV-2 antibodies. His research study involves SARS-CoV-2 antibodies isolated from healthcare workers at YNHH to understand the effectiveness of current protective measures and to understand the importance of possessing antibodies.

Having antibodies, according to Ring, does not necessarily mean immunity to the virus. “It has been shown that antibodies are a two-edged sword,” Ring said. “On the one hand, they can neutralize the virus, and they can prevent it from infecting other cells, but on the other hand … you can get situations where you don’t fully block a virus and you hyperactivate the immune system.”

Understanding these nuances will prove critical in developing vaccines and being aware of treatments to counter dangerous antibody responses.

“Having an antibody that can bind to the viral protein in the lab is a long way from having a cure,” Feimei Liu GRD ’23, a bioengineering graduate student, wrote in an email to the News. “A fundamental understanding of the protective antibody response is crucial for guiding vaccine design and development of new therapeutics that are safe and effective.”

While these teams are using patient samples in their research, other labs are looking at genetic sequencing to answer ongoing questions about the virus. The Yale Center for Genome Analysis (YCGA) is looking at two key areas of genome research: the genes of infected patients and the genome of the virus itself. Like research happening across campus, these labs may prove critical in the development of new treatments and might help explain the disparity in symptoms between patients. 

Shrikant Mane, director of the YCGA and the Keck Biotechnology Resource Laboratory, is looking at which genes are synthesized within cells infected by SARS-CoV-2, how those cells fight back and which methods actually prove effective in combating the virus. 

Studies involving sequencing techniques like Mane’s are being replicated in labs around campus, led by scientists like Guilin Wang, the associate director of microarray research at the YCGA, and Ruth Montgomery, the director of the Yale Cytometry Time-Of-Flight Facility and associate dean for Scientific Affairs at the Yale School of Medicine. 

Regardless of the type of research being conducted, a unique consequence of the outbreak has been a hopeful and exciting shift in research compilation and scientific collaboration. 

“The international sharing of reagents and ideas and suggestions for new ways to approach the experiments has just been unreal,” Montgomery said. “Stuff going up on Twitter minutes after it’s produced in the lab, instead of months later in a journal. It’s astonishing. None of us have ever seen anything like it.”

As Yale mobilizes its labs to fight against coronavirus, research laboratories around the world are doing the same. The novelty of the situation has changed the way people view research and has led to an unprecedented scale of international collaboration. 

In the next few months, Yale laboratories will continue to investigate treatment trials, genome sequencing, antibodies and more, adding its efforts to the millions working towards eradicating the virus.

All non-critical research at Yale has been suspended since March 17.

Rebecca Huang |