RFA grad works on COVID-19 test

Blood test could have wide-ranging impact in fight against coronavirus

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As researchers are working around-the-clock decoding the genetic make-up of COVID-19 in order to develop a safe vaccine that could provide immunity and protect people for decades, a Rome Free Academy graduate is behind-the-scenes working on a blood test in his University of Vermont lab to test who’s been exposed to the potentially deadly virus.

“In my lab we are working on developing a blood test to see if anyone was ever exposed to COVID-19 — the test we’re doing now on patients will only tell if the virus is in their nose or throat, at the very moment they’re getting swabbed,” explained Dr. Sean Diehl, RFA Class of 1994.  

Diehl is an assistant professor in the Department of Microbiology and Molecular Genetics at the University of Vermont’s Larner College of Medicine. For the last 12 years he’s collaborated with the college’s Vaccine Testing Center on projects involving infectious diseases, autoimmune disorders and vaccine development. Diehl’s laboratory had been focused mainly on developing new protections against rotavirus, which is one of the most common and deadly causes of childhood diarrhea, and two mosquito-borne viruses — dengue and Zika — both infect millions of people worldwide each year. With the onset of the coronavirus pandemic, however, the concentration of their work has shifted.

The current test “doesn’t catch everybody, and not every positive test means you have the disease. So a blood test is something we’re working on developing to be able to say if you’re ever exposed, and is it the real deal? It will give us the true extent to how much the virus has spread,” Diehl explained.

As a more accurate blood test is administered to more and more people, Diehl said researchers can then develop a better understanding of what the clinical symptoms of COVID-19 are, such as a cough, fever, or is it asymptomatic? A blood test could also show some people who have had the virus and recovered, why their particular immune system had mistaken it for just a common cold.

Diehl said a high-level blood test of people who had symptoms could show what antibodies helped protect that person. “Perhaps people who had a severe reaction to the virus had a low immune response” and how their antibodies reacted, “just wasn’t enough,” he said.

Back on March 16, the National Institutes of Health launched the first phase of a clinical trial to study an experimental vaccine. It’s being conducted at the Kaiser Permanente Washington Health Research Institute in Seattle. According to reports, as part of that study, 45 volunteers between the ages of 18-55 were injected with different doses of the experimental vaccine — first to see if it was safe, then to evaluate how effective the vaccine was in inducing immune responses.

While Diehl said he was not involved in the Seattle study, he is using the expertise from his research of dengue and Zika vaccines.

In an recent interview for a Vermont newspaper, Diehl said he talked about the first version of the vaccine — the 1.0 — was a matter of taking little pieces of the virus and using that to evoke an immune response. It does not yet contain the entire virus. 

“They’re picking what they think is the best part of the virus to get antibodies from,” the researcher said. “We know the immune system is more than just antibodies, more than T cells, but we don’t know what part of the virus the T cells recognize. It could be that we’ll recognize that we need both of them working together to have protection that will last many years.  We’re trying to understand what the T cell response to the virus could be.”

According to chemocare.com, “The Immune system is a complex network of cells, such as lymphocytes, and organs that work together to defend the body against foreign substances (antigens) such as bacteria, a virus or tumor cell. When the body discovers such a substance several kinds of cells go into action in what is called an immune response.”

According to chemocare.com:

• Lymphocytes are the main types of immune cells, divided mainly into T and B cells. B cells produce antibodies, or proteins that recognize a foreign substance in the body and attach themselves to it. When an antibody locks with an antigen, it marks it for destruction.

T cells are programmed to recognize, respond to and remember antigens. Some T cells can destroy targeted cells on contact and others can signal other cells that their is a foreign body present.

• Macrophages are the first cells to recognize and engulf a foreign body, break them down and present the smaller proteins to the T lymphocytes.

• Dendritic cells are known to be the most efficient antigen-presenting cell type with the ability to interact with T cells and initiate an immune response.

• White Blood Cells: There are different types. Their job is to eat and destroy foreign material.

“Version 1.0 vaccines are just using mainly B cell targets, because in order to find T cell targets, you need to have the full length of the virus growing,” Diehl explained. “This is a brand new virus. We know it’s pretty dangerous, and you need high bio containment to do it (work on a vaccine using the full length of the virus).”

He said, “At UVM, we have a lab that can do that, and we’re working on approval  Once we do get approval, then we can grow it to full strength.”

The importance of working with the virus at full strength is because a weak version may not cause disease, and it can take much longer to figure out, the researcher said. But once the virus is studied at full strength, versions 2.0 and 3.0 of a vaccine may be developed.

Diehl compared COVID-19 to SARS (Severe Acute Respiratory Syndrome), a virus identified in 2003. What was different about SARS was that it only affected a few thousand people, compared to the numbers for coronavirus, but that it was very deadly for those infected, he said. There is no SARS vaccine.

“The SARS virus is very similar to this one,” Diehl said. As for the much fewer numbers of people affected, that’s “why the vaccine for the original SARS stalled. We have version 1.0 — we have pieces of the virus and they did more research on how SARS works as a full, intact virus, but no one was willing to test a vaccine,” he said.

COVID-19 is actually being referred to as SARS 2 because of its great likeness to the original virus.

Diehl said what’s different about the 1.0 version of the COVID-19 vaccine is that usually vaccines take a number of years for research and development, and for human trials to begin. A combination of advanced genetic technology and reductions in “bureaucratic red tape” have greatly shortened the timeline. Diehl would not say for sure when a vaccine would be available, but some estimate it will be ready by the fall.

But Diehl said developing a vaccine for COVID-19 so quickly is setting the bar quite high.

“We have to be able to give it to anybody, at any age, and almost any condition, and it has to be safe, no matter who gets it.  And it needs to protect you forever,” he said. “That’s why it takes so much longer to develop a vaccine than some other drugs.”

“In the first version” of the COVID-19 vaccine, “You’re only trying to take a piece of vaccine, and you can have it reviewed for approval by authorities within a few months, but then you have to prove it’s really going to be safe in a lot of people, and follow them (the people who received it),” he continued. “And you can’t just wait a week — you need to wait a long time to make sure it’s safe for many, and for months.”

Viruses “officially” are not alive.  They need to be inside an animal cell in order to make more copies of themselves and be active.  But COVID-19 is a little more unique in that it’s able to stay on certain surfaces for longer.

“This COVID-19 is kind of inert (it doesn’t really move),” Diehl explained. “When it’s on plastic or stainless steel, in a very controlled lab setting, it’s present after 2-3 days and it’s barely hanging on — it’s barely able to survive. Levels of the virus after that 2-3 days are barely detectable.”

“The basis of that virus — if you’ve seen all the pictures — is like a tiny ball of protein and fat — it’s a fatty protein ball that is a little capsule for mRNA, or genetic information,” he said. “Just sitting on plastic for a few hours, it’s able to stay intact and not fall apart, but it’s not alive.  When we take a swab and apply to cells in a culture, and then the cells are infected, we found that the little balls didn’t fall apart.”

He continued, COVID-19 is “slightly more hardy than other viruses — the previous record holder was the measles virus.  But other viruses like Zika and dengue are not that sturdy. COVID-19 is unique in that it remains or stays intact more than a few hours, and that’s another thing. We don’t understand why.”

Diehl said his university is currently shut down for any other work that doesn’t involve research on COVID-19.

“I have me and two other labs at the University of Vermont exempted on this because we’re working very hard to develop the blood test, and learn what we can about the virus,” he said. “And we’re also trying to develop the infrastructure to do a vaccine trial.”

Diehl said, “There are a lot of scientists dropping what they’re doing, especially those working on other viruses — all work is kind of on hold. We also working to decontaminate masks that health care workers are having to use, a blood test…We’re also working on how to make therapies from the immune response of those who had coronavirus and recovered from it.  All those things will be helpful for us to see if a vaccine candidate will be helpful or not.  Then we can do tests to see if the immune response is effective.”

Diehl earned his doctorate from UVM. He and wife Sandra have two daughters, Jill, 11 and Vera, 9, and reside in Shelburne, Vt.

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