Podcast: What if it’s not COVID-19?

Jim Dryden (host): Hello and welcome to “Show Me the Science,” conversations about science and health with the people of Washington University School of Medicine in St. Louis, Missouri … the Show-Me State. During the first two years that we produced this podcast, we focused entirely on how School of Medicine doctors, researchers and trainees responded to the COVID-19 pandemic. Now as the pandemic, we hope, is receding just a little, we also are reporting on some of the other research, lifesaving and just plain cool work being done at the School of Medicine. Since the pandemic began in the United States, a whole lot of people have been sick with the virus. But with so many COVID-19 patients, sometimes the default diagnosis for doctors has been COVID-19. And in this episode, we bring you the story of a young man who had a cough, a fever, shortness of breath — exactly the symptoms that would be seen in a COVID-19 patient. Michael Moffitt grew up in St. Louis, but he was living in New Mexico when he first began to cough and feel short of breath.
Michael Moffitt: By about day three, the results for the PCR test came in, and they were negative. I thought, “Gee, OK, that’s concerning. What’s going on?” And so I decided to get a second opinion.
Dryden: It took a few more weeks, but eventually Moffitt sought out the expertise of a specialist and made it to St. Louis to be seen by Dr. Andrej Spec, an infectious diseases specialist at Washington University School of Medicine.
Andrej Spec, MD: He was pretty sick, slowly dwindling, progressively getting weaker and starting to lose weight. And it’s a common story. The vast majority of patients kind of go through this story of dwindling and getting worse before they’re actually diagnosed and able to be treated.
Dryden: Spec says when it comes to COVID-19, many of us have the symptoms pretty much memorized: cough, shortness of breath, fever. If you developed those symptoms, what would you think? Well, Moffitt thought the same thing, but he kept testing negative and not getting better. Eventually, that led him from New Mexico to St. Louis to figure things out.
Michael Moffitt: They drove straight through. Fourteen hours all the way back.
Nicole Moffitt: I am not a long-distance driver, by any means. We usually split the drive by two, but we — I mean, we packed everything. We brought our pets. We packed two cars just full of stuff because we had no idea when we’d be back. To this day, I don’t think I could ever repeat that. I drove the entire way through with so much adrenaline. Just kept driving.
Dryden: With assistance from relatives, Michael and Nicole Moffitt managed to drive straight through from New Mexico to St. Louis, but their odyssey to figure out what was wrong had started weeks earlier. The illness that eventually would lead them back to St. Louis began in November, just a few weeks before the first vaccines for COVID-19 would become available. During the weeks between Thanksgiving and Christmas, Michael would spend a good deal of time in doctors’ offices, clinics and emergency rooms in New Mexico. That was where he worked in gas and oil fields when he wasn’t exploring caves.
Michael Moffitt: I was out hiking in the hills outside of Carlsbad, New Mexico. I have a very strange hobby, I’m a caver. I know that’s not a normal deal. And I was looking for caves outside of there, and I noticed that my breathing became labored. And when I got back to my car, I thought, “Man, I feel really off today.” From there, I kept it in my head and I finally — when I got home, a small dry cough had developed and it felt like it came out of nowhere. That was the Sunday before Thanksgiving. Well, that Tuesday, I was at work in the car. And all of a sudden, the dry cough got more and more persistent. And, again, still not to the level of thinking it was anything real concerning, but I thought to myself, “OK, if tomorrow, if it picks up even harder, I’m going to go get tested with the PCR test for COVID.” And so I really was kind of out on my own in the middle of the oil fields out here. So not being around people, I wasn’t really concerned with potential of coming into contact. And about that afternoon, the cough had gotten to the point where all of a sudden I couldn’t even really get a sentence out, called Nicole and said, “I’m going to get a PCR test ASAP.” So I went and got the PCR test that Wednesday before Thanksgiving, I got home. And within a couple of hours of me getting home, the cough got to the point where I had to lay down, and my breathing got labored, and I went into a fever.
Dryden: As they waited for test results, Moffitt and his wife, Nicole, were prepared for delays. In those days, it took some time to get results. Plus, he had been tested the first time the day before Thanksgiving. Nicole Moffitt, who is a nurse, picks up the story.
Nicole Moffitt: We just figured we’d be waiting for a while. And, honestly, we expected that I would have symptoms before we even got that test back. I was working directly with COVID-positive patients and just kind of figured, “Well, if this is COVID, then here we go, we both got it,” and yeah. So then, I don’t know, Michael, take it away.
Michael Moffitt: Yeah. And by the Monday that it hit, because I called my bosses like, “I can’t come to work. There’s potential I have COVID. I haven’t gotten the results back.” It completely knocked me down, especially my breathing, and that’s what really, really panicked me. And I finally said, “I need to get a doctor’s appointment.” And surprisingly, even with the delays and stuff, I was able to get an appointment at the clinic. By that point, it was Tuesday morning is when I got it. By that time, I really noticed the breathing was off. And so when you sit at the table and now I’m very aware of SpO2 levels — basically your oxygen saturation — and they put the monitor on my finger and it was like 92. For people that don’t know what would be considered normal, 98 to 99 is considered normal. And so I was like, “OK, something’s really wrong.” And so the doctor came in, and he looked at me, and the first thing he thought to himself was going to be that you likely have COVID.
Dryden: That was the Tuesday after Thanksgiving. Over the next few weeks, there would be many more trips to see doctors in a number of different settings in New Mexico. He got more medications, took lots more COVID tests, all of which came back negative. But remember, it was late fall of 2020, a time when the first COVID winter was just beginning. The Moffitts say doctors seemed to be seeing symptoms that equated to COVID-19 in just about everybody else, and they couldn’t quite believe the tests kept coming back negative. Meanwhile, Michael wasn’t getting any better. He lost weight. He would sweat through his bedsheets every night. He even had to be put on supplemental oxygen because his blood oxygen had fallen to such low levels. It was the kind of case the fictional Dr. House once might have tried to solve on TV, but this was real life. Moffitt’s symptoms were consistent with COVID-19, but he wasn’t responding to treatment, and he kept testing negative. That’s when they finally pulled the trigger and made the long drive to see Washington University’s Dr. Andrej Spec.
Spec: He was pretty sick, slowly dwindling, progressively getting weaker and starting to lose weight. It’s a common story that we see with our patients who have endemic mycoses.
Dryden: Endemic mycoses are fungal infections that are specific to different parts of the country or the world. After taking a careful history and running some additional tests, Spec found that Moffitt did, in fact, have a fungal infection in his lungs.
Spec: Looking at how many patients actually have a misdiagnosis before they are finally diagnosed, the answer is actually about 80(%) to 90%.
Dryden: On the other hand, in the midst of a pandemic, if somebody presents with a cough and a fever and shortness of breath, I’m not a doctor, but I know what I’m going to think.
Spec: Yeah. It’s the old, “If it looks like a duck, it quacks like a duck and talks like a duck, well, it’s probably a duck.” It’s the difference between thinking fast and slow. There are two types of thinking: There’s the heuristics and then the deep, logical, systematic thinking. And by heuristics, what I mean is these kind of knee-jerk thought processes. And if I see a patient in the ER or on the floor and they’re coughing and they have a shortness of breath, most likely the answer is going to be COVID. And that’s the case in most situations, but not always. And so that’s the moment where it’s, “When do you learn to switch from one thought pattern to the other?” At some point, you’re going to realize that, “Well, I just went down the wrong path.” They need to be able to catch yourself, stop yourself, move back to the beginning, and start to think in a systematic way, where you start to break it down and try to reassess all of your assumptions so you can hopefully get back to the right place.
Dryden: This particular patient had a fungal infection. It may have been Valley fever caused by a fungus that could have blown into his lungs when he was working in the oil and gas fields. Or it may have been histoplasmosis, a fungal infection associated with exploring in caves. Caves have bats, and bat droppings, or guano, often contain the infectious fungus.
Spec: Because Histoplasma lives in bats and is spread by bat droppings. And so those pieces of history are very helpful, and they were instrumental in us making that diagnosis, but the problem is that those are individual pieces of information that are usually not available to physicians, especially during a peak of a COVID wave. And for them to be able to get all of those pieces of history from a patient is probably not going to happen, and it’s probably an unrealistic expectation. A lot of patients do have a history of serious exposures such as spelunking or a couple I treated not that long ago cleaning out their home after a flood, so all that rich, loamy, nitrogen-rich mud was just ankle-deep in their house and they were literally mucking it out themselves, or cleaning out an old barn or things like that. But in reality, about 60% of my patients who have proven disease, that I manage and get them better, don’t have a good exposure. They often are just very frustrated and are constantly asking me, “Well, where did I get this?” And what I usually like to tell people is that it’s a little bit — and here I’m going to date myself — it’s like that Police song from the 1980s, it’s “Every Breath You Take.” By the time you’re 18 years old and living in St Louis, about 70(%) — 69% is the number — but 70% of people have been infected with Histoplasma. And it was either asymptomatic or it was that cold that just took a little too long to kick. Normally, most colds are five days. Whereas for histo, that may have been that cold that took three weeks to go away or four weeks or even six weeks. And you were told maybe you have a postnasal drip, maybe you were told you had bronchitis. That’s kind of what we tend to see the most, and we don’t tend to find a strong association. And so there really isn’t a golden arrow that we can use that kind of pinpoints like, “This is it.” So I think really the most important thing in this situation is that switch that I was mentioning before. It’s a switch from heuristics to slow thinking. When you are starting the process, it’s reasonable to start treating for COVID. But when you’re doing it and things are just not getting better or the patient is really dwindling or the patient really starts to lose weight, which is kind of more of a common thing with fungal infections than it is with COVID, then you should start to broaden your differential and start to look for other things.
Dryden: After a few weeks of living with this mysterious illness, Michael and Nicole Moffitt finally decided it was time to shift their thinking. It was a Friday, the Friday before Christmas, and his blood oxygen levels got dangerously low.
Michael Moffitt: When it really hit the fan was the Friday of the week before Christmas, we were sitting on the couch —
Nicole Moffitt: At 89%.
Michael Moffitt: What happened was we were watching “All Dogs Go to Heaven,” and we were sitting on the couch —
Nicole Moffitt: Bringing back the cartoons, happy movies.
Michael Moffitt: Right. We were just trying to watch, we were just trying to watch cartoons at that point, and I wasn’t eating at that point. I dropped about 30 pounds in three weeks, and I was pretty bedridden at that point. And so I walked from the bedroom. As soon as I got back from the couch, my breathing was pretty labored. So my breathing was pretty labored, and it dropped down to 82, and I was like, “OK, the fan has hit. I need to go to the emergency room.”
Dryden: The trip to the emergency room netted him portable oxygen and more drugs to take home, and it also got the ball rolling on a referral to Spec. After weeks of mistreat, that appointment with Spec identified the problem. And that same day, Moffitt was admitted to Barnes-Jewish Hospital, one of the academic hospitals affiliated with Washington University School of Medicine.
Spec: He was being told it’s COVID and, “Well, maybe it’s not COVID, maybe it’s Valley fever.” In New Mexico, that would be the case. Valley fever is predominantly what we see over there. We almost never see histoplasmosis there. However, he has been spelunking in the caves. And the caves have bats, but there’s no Histo over there. However, there is in Central America, and the bats migrate. And as the climate changes, all of those things are changing because bat migration patterns are different than they used to be. There’s tons of data now that we’re finding that, species of bats, they used to be in one place are now in a different place, and Histo follows along with that. In his situation, he was being treated with fluconazole which is a drug of choice for coccidioidomycosis, which is the Valley fever, but what he had was histo. And fluconazole is very much inferior for histoplasmosis. Also to add to that, he had severe disease. He was having trouble breathing. And if you have somebody who’s got oxygen and they’re progressively losing their ability to breathe, starting a drug that’s going to take seven days to start working is just not appropriate. And so what we did is we admitted him, and we gave him amphotericin, which is an IV drug that starts to work within minutes to hours, and so we got a rapid response within a couple of days.
Dryden: Moffitt spent Christmas in the hospital at a time when it was crowded with COVID-19 patients, but it was a fungal infection that landed him there and kept him there.
Michael Moffitt: I spent my Christmas Eve and my Christmas Day in the hospital. I could only have one visitor a day. So basically, again, it would have been Wednesday to the day before New Year’s Eve. It cleared up. It’s just bizarre going from 0 to 180 and 180 back to 0.
Dryden: Spec says he’s treated several patients who had similar experiences thinking, quite reasonably, that they had COVID-19. But it wasn’t a virus that caused their problems, it was a fungus.
Spec: If you think that your patient has never been in a place where there is Histo, well, you don’t test for Histo. And these are diseases that don’t really just kind of jump out at you, you have to think of them and then test for them and then treat for them.
Dryden: When you talked about how 69% of the people of this region have had a histoplasmosis infection, I am assuming that means that for most people they get better on their own, and these serious sorts of infections are rarer, or how does that shake out?
Spec: So most people, greater than 95% of people, are going to be either asymptomatic or in that really bad cold/annoying pneumonia stage where it kind of just lasts for a long time and then eventually goes away. There are a few ways that rule gets broken. One is if the infection becomes severe and become a severe pulmonary infection, where you get a severe pneumonia that can be lethal and it can be — as in the situation that we were talking about where he needed to be on oxygen and was really — even on oxygen — was still having a lot of trouble breathing. The other way it breaks down is through dissemination. Different ones will go to different places. They go to the bones, the liver, intestines, brain, skin is also a commonplace. And when that happens, then we need to have much more aggressive treatment.
Dryden: So if you’ve been coughing, feverish and short of breath, you may have COVID-19. You probably do. But if you keep testing negative and not getting better, well, it may be something else. Michael Moffitt got lucky. He got better.
“Show Me the Science” is a production of the Office of Medical Public Affairs at Washington University School of Medicine in St. Louis. The goal of this project is to introduce you to the groundbreaking research, lifesaving and just plain cool work being done by faculty, staff, and students at the School of Medicine. If you’ve enjoyed what you’ve heard, please remember to subscribe and tell your friends. Thanks for tuning in. I’m Jim Dryden. Stay safe.