Rarely in the history of the world have so many scientists been at work in so many places simultaneously trying to find treatments and hopefully a vaccine for a single disease. The new coronavirus isn’t the first pandemic the world has seen, and like many viruses which came before it seems to have few boundaries. With its airborne transmission, it has attacked young and old, every race, and every sexual preference on every continent except Antarctica. In a few months, COVID-19, the disease caused by the coronavirus, has already killed 138,000 people worldwide — and counting.
Of the pandemics over the last century, certainly the HIV/AIDS pandemic has been deadlier, killing 32 million people since 1981, though death tolls have leveled off as new treatments made the disease far more manageable. While the “Hong Kong Flu” of 1968 had a low mortality rate, it still resulted in the death of 1 million people worldwide. The so-called “Asian Flu” of 1957-1958 originated in China and wiped out at least 1.1 million people, including at least 116,000 in the U.S. alone. But those don’t compare to the influenza pandemic of 1918 — often called “Spanish flu” — which ended the lives of 50 million people. Unlike COVID-19, that flu strain routinely struck down completely healthy young adults.
The nature of each of the aforementioned viruses is very different. Understanding what those differences are and answering all-important questions about the specifics of COVID-19 is the key to finding treatments and a vaccine.
This month, the National Institutes of Health, National Institute of Allergy and Infectious Disease awarded a contract to the Tulane National Primate Research Center — located in Covington — to test potential vaccines and treatments to combat this ubiquitous virus. The research beginning there in just a few weeks will attempt to answer many vexing questions.
“We are looking to really develop the non-human primate model from which we can begin to understand such things as the mode of transmission, the route of exposure, and why some people are getting mild doses of the virus, while others are dying,” explained Dr. Chad Roy, director of infectious disease aerobiology at Tulane National Primate Research Center and the project’s director. “We will be utilizing three different primate species closely aligned with the human population, for testing. This includes the rhesus monkey, the rhesus macaque, and the African green monkey. We will be testing both treatments and vaccines, and at this moment there are already over 70 potential vaccines.”
Testing key to vaccine approval
Animal models have always been critical, and in fact private labs all across this country working on their own therapeutics and vaccines are required to show results in monkeys before any FDA approval could ever be granted.
Studying the immune responses in primates give a much clearer idea of why and how people are infected, and gives us a window into determining whether a repeated onslaught of the virus makes it more difficult for our own immune systems to fend off this particular coronavirus.
“The healthcare workers, for example, certainly have higher exposure to this virus,” said Robert Garry, M.D., a virologist and professor of microbiology and immunology at Tulane Medical School. “They are around extremely sick people and they are around them constantly. Eventually, the immune system breaks down, as higher and higher concentrations of the virus are getting deeper into the lungs of those who are on the frontlines of the ICU’s. There’s been a paper or two published in China already about the difference in antibodies from those who had minor symptoms or were asymptomatic as opposed to those hospitalized with serious symptoms. The immune response looks to be much stronger in those who had to stave off extremely life-threatening symptoms. That’s why in obtaining antibodies from those who have already had COVID-19, we gather those from the patients who were hospitalized in serious condition.”
The 4,000 animals who live at the primate center are a hardy bunch. They and their predecessors there have been used in biomedical research for 50 years, so much is known about their genetics, and it’s why they will play a very important first-step in the research.
“We initially need to simulate how this virus affects a normal healthy person, so we use very healthy primates,” explained Dr. Roy. “These are animals very close to us genetically, so their response to treatments and new vaccines is very closely aligned with ours. Once we establish how a healthy non-human primate responds, then we can factor in comorbidities that arise out of pre-existing conditions in humans, like hypertension, diabetes, COPD, and morbid obesity.”
How the virus behaves
Ever since 1939, when an electron microscope imaged the first virus, (Latin for poisonous slimy liquid), scientists have known that the very nature of a virus is to change or mutate in response to its environment. It is why people can be reinfected with the flu in spite of getting a flu vaccine. A virus’ ability to rapidly mutate lets it escape from our immune system’s memory. That can make a broad, effective vaccine challenging to produce.
“Mutations are always a possibility,” said Roy. “But I do know that a number of the vaccine products are being developed around a shared commonality, so that even if there is a mutation, the vaccine would still be effective.”
There are certainly arguments made by virologists that this novel coronavirus has no need to change.
“Look, this is a virus which is well adapted to humans,” explained Dr. Garry. “It’s been spreading unchecked for many months now across the globe. There is no advantage for this virus to start killing off its host (humans), because it’s been very effective. That leads us to believe that this virus would become less virulent over time, not more virulent.”
Assuming COVID-19 will continue to spread, it’s important we learn just how the contagion goes from one individual to another, why everyone responds in a different manner, and how long the virus actually stays in the body, even after symptoms abate.
“You know, from some of the animal models that we’ve done thus far, it looks like the virus tends to sequester in the body,” said Roy. “We’d like to know if the body switches over to a true convalescent state where there’s no more virus, and no further possibility of spreading the virus, or becoming reinfected. Those are critical questions we still need to answer.”
It’s a question that’s now been posed in light of China’s lifting of its own lockdown, only to see a re-emergence of COVID-19 cases within the first week.
“We know that you can shed virus for 2-3 weeks after your symptoms resolve,” said Garry. “But does this mean one is still infectious? It’s likely shedding could last a while, but is it days or weeks? We don’t know, and it’s something for which we need an answer before we send anyone back into the community. I will say this … you definitely should mask up during this post-symptom convalescent period. It’s not the time to visit grandma.”
Reactivation has been seen before with Ebola, where patients were supposedly recovering, only to find the virus in what are called “privileged” sites: the brain and testes, which respond less to traditional anti-virals.
“There’s no evidence yet that this is happening with COVID-19, but it has happened with SARS, and with AIDS, where there’s sexual transmission,” recounted Garry.
Although intelligence officials are reportedly investigating whether the coronavirus originated in a lab, there is no evidence to support that this virus is anything other than natural.
Given that, it brings up questions about species to species transfer, which The Lens put to both doctors. If the virus originated in animals, animal to human transmission has already been demonstrated. But what about the reverse? Until the Bronx Zoo announced that four tigers and one lion had been infected by a zookeeper with COVID-19, it wasn’t discussed much.
“I’ve certainly heard this zoo story,” Roy said. “However, I haven’t read any scientific papers about this, and it would need to be experimentally figured out to see if that infectivity route is a possibility. I’m just not familiar with that particular species to species transmission.”
“It’s an interesting question because some of the other coronaviruses have infected cats, and tigers are just big cats,” Garry said. “China has reported that some domestic animals like cats had become infected — not so much dogs. And, it’s probably highly unlikely that you would give it to your pet if you were sick. But, of course, the zoo thing raises questions. Let’s put it this way, it’s certainly not an efficient transmission like we see amongst people.”
There are so many unanswered questions at this stage of the game, which is why research needs to begin sooner than later. The quest for a vaccine is central to solving the problems with the spread of this disease, and ultimately our going back to a semblance of life as we knew it. So, how would a vaccine study work with primates?
“We would try to stay consistent with a human schedule for vaccines,” Roy said. “So, a primary dose, then a waiting period of 30 days before a booster, then another 30 days and maybe another booster. Then we would wait four or five weeks for a challenge study to get an idea of the immediate immunology associated with a response to that vaccine. The animals will be constantly monitored for heart rate, fever, breathing, and we have incredible resources here … PET scanners, CT’s, you name it.”
With the world demand for a vaccine at a fevered pitch, the word “timeline” comes into play, but it’s difficult to put success into a specific number of months.
“This won’t be an easy virus for which to find a vaccine,” surmised Garry. “But, I’m one of the people who thinks it’s possible, if we put everything we have at it in a Manhattan-style Project, pulling out all the stops. That means getting out of our own way with regulatory issues. It’s important to test treatments and vaccines simultaneously, and certainly test drugs on the sickest patients. And, if we do find something effective, we need to gear up manufacturing very quickly. We spent $2 trillion on a stimulus package, so if we spend a fraction of that, we should have a vaccine.”