New Haven Register (New Haven, CT)
What we don’t know after six months of COVID-19
It’s been four months.
It was six months ago that the first case of the novel coronavirus was confirmed in the United States, but it was March 6 that Gov. Ned Lamont announced the first patient in Connecticut.
Four months, Lauren Ferrante explained, is not a very long time in which to understand and fight a pandemic.
“There’s a lot we don’t know yet
because COVID is a new disease,” Ferrante said. “I mean, we’re only in early July now. So we’re just starting to capture what patients’ outcomes will look like after their COVID illness.”
Ferrante is an assistant professor of pulmonary medicine at Yale New Haven Hospital, but she also helps run the Comprehensive Post-COVID Care Center at Yale, which is attempting to treat and track COVID-19 patients’ recovery, long-term.
“There are patients who had moderate disease where they were in the hospital and maybe just on some oxygen, but did not need to go to the intensive care unit. And there were patients with severe COVID disease who were critically ill in the ICU on a
lot of oxygen support or perhaps even on a ventilator,” she said. “So, one of the questions that we’re interested in exploring, both clinically and in research, is what the long-term outcomes look like for each of those patient populations.”
Known unknowns
The disease is so new, Ferrante said, that “long-term” isn’t something that really exists. There haven’t been studies going back decades, like there have been with influenza and measles.
“There’s still a lot we don’t know,” she said.
Terri Hough would agree. She’s head of the pulmonary critical care division at the Oregon Health and Science University. She also helped design the CORAL project for the National Institutes of Health, which is looking at long-term care of COVID-19 patients from a variety of perspectives, including clinical, epidemiological and biological.
“There’s these aspects of disease we just don’t know about,” she said. “If your lung function is really bad, do your lungs recover? We don’t know yet. We don’t know for COVID, can you get it again? Are you at risk for recurrent infection? We don’t know that. Do you end up back in the hospital three months later with sepsis and die?”
Hough also pointed to genetic questions, and the role of social factors. Does blood type play a role in patient outcomes as some research has suggested?
“Are there going to be genetic predictors of this?” she asked. “Probably.”
The disease is so new to science and medicine that “recovery” is a moving target.
“There are certainly a few factors or a few facets of COVID-19 that are
different than other kinds of pneumonia or other kinds of severe infection,” Hough said. “Specifically, how much it targets the lungs, how severely impacted the lungs are and how long recovery takes that’s pretty unique.
Ferrante said that to judge recovery, she and her colleagues ask patients to compare their ability to live their lives before and after infection.
“What studies have shown is that even if those pulmonary function impairments resolve the patient may still have problems with physical function, they may not be able to do the activities that they could do before they were in the ICU,” she said. “They may be short of breath climbing stairs or going for a brisk walk, whereas they were completely functional beforehand and had no problems.”
Shortness of breath
One of the questions Ferrante is seeking to answer is, why do patients complain of shortness of breath even after their lung function tests come back with no problems?
“The most common symptom that we’ve heard about is persistent shortness of breath, even though they had COVID three months ago, and even though they may not have been in the hospital,” she said.
Imagine a patient. They were diagnosed with and treated for COVID-19 months ago, and though they had been sick they had never been sick enough for an extended hospital stay.
Now, months later, their lung tests — pulmonary function testing — show healthy lungs. But when they go through physical therapy, or try to walk up stairs, they complain of trouble breathing.
Ferrante said it’s surprising in two ways. First of all, the lung function is better than expected. But then why are patients short of breath?
“It’s so soon after the disease, I would have thought that they still had lung function impairments and that’s
a partial explanation for their shortness of breath,” she said. “But already even after just one to three months, their pulmonary function tests are normal, but they’re still very short of breath.”
The way to better understand questions like that is “to have a longitudinal cohort of patients that you follow over time,” Ferrante said. “And even with that longitudinal cohort, we’re only at the one-month follow up essentially, if you think about the patients that [were] discharged at the end of May, so there’s still a lot we don’t know. And the coming year will be very informative as these patients are tracked over time.”
Unknown unknowns
COVID-19 is primarily a pulmonary disease, and there is a lot clinicians and researchers do know about how disease affects the lungs.
“There is a lot we know about how to manage ARDS (acute respiratory distress syndrome) and hypoxemic respiratory failure, and we all need to make sure that we’re doing what we know works and that’s how patients get good care,” said Ferrante.
What’s different with COVID-19, Hough said, is that the pandemic is creating large numbers of sick people in a short time.
“As an epidemiologist with statistical training, I understand that that range is a function of number,” she said. “So the more patients you have, the more likely you’re going to see a more dramatic range of symptoms and manifestations.”
One of the most important lessons Hough said she has taken from the pandemic, is to know what you don’t know.
“I think we are going to see that there are quantum changes in outcome with age that were not based on a patient’s physiology, but based on a physician’s practice,” she said. “Maybe
we thought we knew more about this disease than we did early on.”
Her work with the NIH’s CORAL project started looking at 1,500 patients over the course of a month during the height of the pandemic. It’s next phase is to follow the outcomes of patients from their first admission to the hospital through the recovery process, taking biological samples along the way.
That kind of work hasn’t been done yet — there simply hasn’t been the time — which is why she stressed the “need to remain humble about all of the areas that we don’t know for sure.”
“It’s hard when you have 100 of these patients in a row and you’re working too hard, and you’re scared, and you’re wearing all this crappy equipment that’s hot, to step back and say, ‘Why am I making the decisions that I’m making and how strong was the data that it’s based on?’” she said. “To think like a baby and say, ‘You know what? I’ve now seen one case, so I should not be anchored to the idea that I actually know that I should do something different than my usual care.’”