April 10, 2020: In a wide-ranging discussion, UF's Emerging Pathogens Institute Director J. Glenn Morris, M.D., fields big-picture questions about the COVID-19 pandemic unfolding nationally and in Florida.
The Emerging Pathogens Institute was formed in 2006 to bring researchers across disciplines together with the goal of better understanding and anticipating new disease-causing microorganisms that affect people, plants and animals. Much of its research is focused globally, with an eye toward what might affect the State of Florida. But for the first time, the COVID-19 pandemic has brought a widespread outbreak right up to the institute's doors.
As COVID-19 spread from country to country, then crossed continents and arrived to the U.S., the EPI prepared by readying a test one of its researchers had developed years earlier for an environmental survey to detect coronaviruses in Florida bats. Having this basic research ready to be deployed in late January allowed the institute to collaborate with researchers and entities across UF's campus to offer early research-based COVID-19 testing to community members.
Since its inception, the EPI has been under the leadership of J. Glenn Morris, M.D., M.P.H & T.M. Here, he reflects on the beginnings of the COVID-19 pandemic, what went wrong with U.S. testing efforts, how the disease spreads and manifests, and how his institute is working to better understand and mitigate the damage wrought by SARS-CoV-2, the virus which causes the illness known as COVID-19.
Here at the Emerging Pathogens Institute, we spend a lot of our time watching for new pathogens, and we were monitoring the emergence of COVID-19 from the very beginning. Our level of interest went up substantially as this new coronavirus spread rapidly in human populations, and was linked with serious illnesses. There are four strains of coronavirus that circulate routinely in human populations and cause mild cold-like symptoms. But when coronaviruses originate in other animals and jump into humans, they can sometimes cause severe illnesses such as what we’ve seen in the past with the emergence of severe acute respiratory syndrome and Middle Eastern respiratory syndrome. Coronaviruses in particular have an uncanny ability to pick up the genetic material needed to move into people and cause serious disease.
We at the EPI are particularly concerned about the transfer of microorganisms from animal species to humans. These are what we call zoonotic diseases. There is a history of new coronaviruses coming out of China, and this one was associated with live animal markets which are a classic venue for transferring viruses from animal species to humans. Some of the more dangerous coronaviruses to humans have originated in bats. When this new virus showed up, and then the Chinese published the sequence, it clearly identified it as a coronavirus that likely originated in bats.
One of our faculty members, John Lednicky, is recognized as one of the best virologists in the world and he has extensive experience working with coronaviruses, particularly Middle East respiratory syndrome and severe acute respiratory syndrome. Four years ago, he isolated coronaviruses from bats here in Florida, just to survey and see what is out there. In late January, he put together an assay for the new coronavirus, SARS-CoV-2, that would permit its identification.
At about the same time, our concern began shifting over to creating models of how this microorganism might spread and be transmitted. One of our members is a world-class biostatician, Ira Longini, and he has been very active in working with World Health Organization and Centers for Disease Control and Prevention in this regard.
Of those who are infected with the novel virus, probably half get no symptoms at all. But for most of the remainder, they may get mild symptoms akin to a bad cold. Kids may have a runny nose or minimal symptoms.
Some 20 percent of those infected may have more serious illness. For about half of these cases, and this varies depending upon which studies you are looking at, some will have the virus get down into the lungs where it causes breathing problems and the person will require hospitalization. And then for a small percentage of those patients, there may be serious breathing challenges where they need the help of a respirator.
The symptoms are diverse, and age seems to be a major driver as to whether you get mild or no symptoms, more moderate to severe symptoms, or very severe symptoms. The other issue is whether someone has an underlying disease that impedes their immune system from responding. People who are hypertensive, diabetic, or have underlying chronic diseases appear to be at greatest risk.
While our attention has focused on respiratory symptoms, there are many patients who will develop diarrhea. This virus gets into the upper respiratory system, then the blood, then the intestinal tract where it causes diarrhea. Virus has been found in stool and is likely also present in urine. The more severe cases may be more likely to experience diarrhea, but there are also some instances where the primary symptom is diarrhea.
This is a highly contagious virus, and it can spread by a variety of means. The primary route is probably through carriage of the virus by large droplets coming from the respiratory tract when you sneeze or cough. These droplets fall out of the air fairly quickly, and contaminate the immediate area around you – leading to the recommendation to stay 6 feet away from other people as part of social distancing. But the virus is also capable of what we call airborne transmission. In airborne transmission, viruses are in very small droplets that don’t fall to the ground, but just drift in the air for hours at a time. Social distancing is important, but it needs to be recognized that because of airborne transmission, there is a possibility to become infected at a greater distance, in particular when you are in a crowded room with a lot of different people. The infection can also be transmitted when virus in diarrhea is aerosolized – which occurs primarily when a toilet containing diarrheal stool is flushed.
About half of the people who are infected are asymptomatic, yet we know that they can carry and transmit the virus. People who are infected may also be spreading the virus for a few days before they become symptomatic, and even weeks after their symptoms have resolved. Asymptomatic carriage is likely a key factor in the speed with which this virus spreads to large numbers of people.
It makes it very difficult. The problem we’ve got is that without widespread testing we don’t know what is happening in terms of infection risk, and it becomes very difficult to make appropriate, careful, well-reasoned decisions on what level of isolation is appropriate at any given time or place.
In this sense, we are basically flying blind in trying to limit spread of the virus. Because of the lack of readily available and widespread testing, we don’t know where the virus is; whether there are a lot of people infected and there is a need for continued aggressive shut-down-everything measures, or whether infections are rare, and it may be possible to consider lifting some curbs on movement of people. The measurements of what is in the community should be what guides the public health response, and right now we are grappling with what to do in the absence of that data.
To totally suppress transmission you really have to do some heroic stuff, as we are seeing now in the United States: shut down your businesses, put everyone in lockdown. While this is essential in slowing initial spread of the virus, a lot of uncertainty remains about when and how such restrictions can and should be lifted. The South Koreans did this very elegantly, because they knew where there were clusters of infection, and when viral numbers started going up they were able to put in place targeted interventions. You look at Singapore, Hong Kong, Taiwan – these are the places that had broad and robust testing. They were able to identify cases, monitor and quarantine them with almost surgical precision. In contrast, here in the States we have largely been flying blind.
In Florida, the disease is of greater concern because of our elderly population. People move here to get away from the cold and we have a lot of retirees, making Florida a high-risk state. We don’t know for sure the effect of climate yet, there are mixed messages from the available data. It’s possible that warmer weather may reduce some of the transmission, but this may be because in warmer weather people stay out-of-doors more. It may not be the actual temperature that matters but the tendency to not be in small closed rooms.
Diagnostically, it creates a clinical dilemma when testing resources are limited. In the earlier phases of the disease it really is not possible to differentiate influenza and COVID-19. Test are necessary because there are a lot more similarities than differences. Speaking as a clinician, someone who comes in with a fever and flu-like symptoms may well have the flu or may have COVID-19. In the absence of tests one is never quite sure. But there can also be coinfections. Studies show that infections with both viruses have occurred. Just because you are positive for the flu does not rule out the possibility that you also have COVID-19.
In terms of symptoms, COVID-19 is more likely to develop a diarrheal component than flu. But that tends to occur later in the illness. COVID-19 is a potentially more serious illness for the elderly. Reported mortality rates with COVID-19 vary widely from region to region, but, in general, it appears that COVID-19 has at least a ten times higher mortality than influenza.
The South Koreans have emerged as the folks who have done far and away the best job. They have had drive-thru sites accessible for large numbers of tests for whoever wanted one, with results by text message within a matter of hours. By identifying these cases, infected individuals could be isolated and taken out of circulation.
Questions have been raised about the effectiveness of closing schools. You do stop transmission among school kids which can be an important route. But if all the kids go home, then the grandparents are the ones taking care of them and the parents are staying home from work. This creates another set of problems which may increase some of the issues related to transmission. Singapore has had excellent control of the disease, but they never closed their schools. They had great testing, they had strong contact tracing, so that when cases occurred, they were able to track them down. In this setting, they never felt they needed to move forward with closing schools.
We are replicating some of the approaches that were initially tried, or put in place in China; slowing down the movement of people, from region to region and ultimately going down to the level of placing restrictions on people leaving their homes. But some countries were better able to decide when and where restrictions should be put in place due to data from testing. Areas with aggressive testing had the ability to more carefully manage these interventions. Because of our lack of testing in the U.S., we really missed the boat.
Our testing in the U.S. got caught up in bureaucracy. The CDC initially said everything had to go through them. There were few tests being performed, combined with a lengthy turn-around time on getting results for the testing that was done. Then CDC began distributing tests to the state health department laboratories, but it turned out their kits had issues. There was not a strong initial push to get the test out to commercial laboratories, or to get it integrated into the overall medical care system. Nor was there a strong effort to create the type of drive-through testing that we see in South Korea and other parts of Asia. Initially, institutions were actively discouraged from developing tests other than the test developed by CDC; as the epidemic progressed, the Food and Drug Administration did allow for development of alternative tests, but the associated bureaucratic requirements were such that there was little incentive for further test development.
We developed our own test here at the EPI back in late January. But the problem is that we are not a CLIA certified laboratory: even when the FDA started lifting regulations, they said only CLIA certified laboratories could do patient testing. I should point out, there is nothing magical about these tests. Basically, it’s an rt-PCR reaction which is very easy to do. It requires skilled technicians of course, but it’s not magical. The key is identifying the primer sets used to identify the virus. We had already identified what we thought were optimal primer sets. Our primer sets were similar to what were being recommended in Europe. But they differed a fair bit from those recommended by the CDC. We had an alternative assay, we had the capability of running a fairly good number of samples, but because we were not a CLIA certified laboratory, the data from our testing could not be used for clinical decision making.
The FDA later said that hospital labs that were CLIA certified could develop their own tests, but the problem was that capabilities for developing these tests tended to be at the academic level, within academic institutes such as the EPI. As a result, although belated efforts were made to expand testing, it did not take off. And we are just now beginning to see testing ramping up. The next problem was that the nation as a whole is now low on the supplies needed to make these tests.
At the EPI, we are testing on a research basis. The people we test sign a consent form saying they understand that this is not an official FDA-approved and certified test. But nonetheless, we have been able to do a substantial amount of testing which is at least helping us to understand transmission patterns in our immediate area. But we are running into the same problems as everyone else: the supplies are limited.
We are doing testing on selected populations here in Gainesville, as well as in Jacksonville and The Villages®, a retirement community south of here. It is allowing us to get a sense of transmission dynamics, and explore factors that drive transmission and occurrence of illness, particularly for populations at increased risk of having severe illness.
The CDC and the federal government are now saying not to test unless someone is sick, due in part to the lack of availability of tests. If these guidelines are strictly followed, we miss the asymptomatic cases, which can be contributing substantially to transmission of the virus. Because of this, in our testing we have focused on persons who are concerned about possible exposure to the virus, but who are not symptomatic, or have only mild symptoms. By doing this, we hope to get a better picture of overall transmission patterns.
Point of care testing is widely available internationally. It just has not been approved by the FDA yet for use in the States. That would make a huge difference, if they could bring that in. One issue is the size of this country; with a population of over 300 million, there are a lot of people who might need, or want, to be tested. That is a lot of tests. We’re just late on everything.
There are reports of people becoming reinfected, but I think that most of that is simply people who remain culture-positive for multiple weeks after an acute infection. It’s not so much that they became infected again but that they are still infected with the organism that caused the original illness. There are reasonably good data that you likely get at least a year or two of immunity out of a case. It is almost certainly not life-long immunity.
We will find a vaccine, it’s just going to take a little bit of time to develop and optimize it so that it will last for as long as possible. The coronavirus has been associated with cytokine storms, where your immune system goes crazy. We must be careful with vaccines because we don’t want to create a situation where the vaccine makes an infection worse by stimulating the immune system. It’s a slow, methodical process that may take one to two years – or longer.
I think there is a high likelihood this will become endemic and seasonal. Coronaviruses have probably been endemic and seasonal in human populations for hundreds of years, and we see this type of pattern with the “benign” coronaviruses that cause mild “colds” and other respiratory symptoms.
There is research waiting for us at all different levels. One is to understand basic transmission patterns of the virus, and to begin to get a feel for whether there is endemicity and what type of seasonal patterns might emerge. These types of data will also help in development of mathematic models, to predict spread of the disease and assess the public health impact of interventions. At the diagnostic level, we are also working on alternative tests for infection, and development of assays for the presence of antibodies against the virus. These latter data will be critical in assessing the level of “herd immunity” to the virus – which, in turn, will be an important element in assessing the risk of future epidemics.
At the basic science level, we have isolated the virus from patients in our community. We are sequencing it from multiple patients and studying factors from both the host and the virus that may account for differences in severity from patient to patient. We are also looking into therapeutics, and working closely with the UF Institute for Therapeutic Innovation at Lake Nona to screen for current drugs that show activity against the virus.
We are also looking at underlying receptors in the virus, because then we can try to block them and hopefully reduce the severity of the illness. There is a wide range of activity. This is what we do for a living, study new viruses and pathogens. At the EPI, we have the capability and the expertise. This will be a major area of research for many years ahead.
Edited by DeLene Beeland; portrait of Dr. Glenn Morris by UF Health Communications.