When the coronavirus pandemic hit the United States in the winter, it was like a “tragic bucket of cold water,” according to Vice Admiral Dr. Matthew Nathan, the former surgeon general of the U.S. Navy.
Medical professionals like Nathan were astounded by the thousands of people - particularly those in high-risk brackets, including elderly and diabetic individuals as well as patients with heart disease and other preexisting conditions - who were succumbing at record rates to the novel virus.
Questions and misconceptions about COVID-19 were aplenty. What was known for certain, though, was that the virus mostly attacked the lungs.
Over time, Nathan said, physicians recognized the virus had two main phases among its most serious patients: It first created a bad respiratory infection and then caused the immune response to go into “hyperdrive," enflaming cells and leading to potentially lethal side effects.
“It was ravaging their bodies,” he said. “That’s what caught our attention first: People were going in with what appeared to just be a very bad flu and not surviving it, requiring ventilation.”
There are more certainties about coronavirus now. However, questions remain about its lingering effects among patients, both severe and moderate.
Months into the pandemic, a new group of individuals has emerged: so-called coronavirus “long haulers,” people who contracted COVID-19 in the early stages of the public health crisis, may or may not have been hospitalized and are still experiencing symptoms linked to the virus.
Fatigue, brain fog, dry coughing, shortness of breath and even cardiac rhythm problems are a few of the lasting symptoms long haulers are reporting, according to Dr. Zeina El-Chemali, the director of neuropsychology clinics and training at the psychiatry and neurology departments at Massachusetts General Hospital.
“The patients we are seeing are not necessarily hospitalized,” the Boston doctor said. “They had COVID-19, stayed in their homes, maybe with a fever. Then months later, they feel their symptoms aren’t going anywhere.”
El-Chemali, who teaches at Harvard Medical School, has been researching coronavirus’s impact on people’s brains and the neurological symptoms of long haulers. She called the lack of information on the long-lasting effects of the virus concerning.
“It’s not going away," she said.
In his current role as a Harvard University fellow, Nathan has similarly been looking at the mysterious group of long hauler patients, trying to understand why so many individuals who came down with coronavirus more than five months ago continue to experience such a wide array of symptoms.
Nathan has been communicating with doctors in Los Angeles, New York and Seattle about long haulers and studying the degree of their symptoms. He pointed out that people need to recognize the world’s still in the “infancy” of the pandemic, so information will be lacking.
“Really, we’re only about six months into a full-tilt study since the world’s come together to compare notes,” Nathan told MassLive.
It is difficult to try to quantify the number of coronavirus patients who wind up with long-lasting complications, according to Nathan. The doctor noted, though, roughly half of the individuals hospitalized with more severe symptoms become long haulers, amounting to tens of thousands of people.
Pulmonary specialists and cardiologists who treated people with COVID-19 early on in the pandemic, have just recently started to see some of their patients come back with significant impairments, according to Nathan.
Such individuals went to the hospital months ago to be treated for the viral respiratory infection. They may have been put on oxygen, remdesivir or even a ventilator, and in many of their cases, the virus left them with bodily damages that medical professionals are unsure how long will last.
What researchers and doctors do know is that COVID-19 significantly impaired the patients' lung functions, to the point that they are still dealing with breathing issues and other complications.
“Many of the patients who had moderate to severe COVID infections - those were mostly the patients who got laid up in the hospital - were able to walk out of the hospital, and everybody went, ‘Phew, boy, that was a close one,’ " Nathan said. “Then only to find that they had a residual damage to their lungs.”
‘It’s kind of like a slap in the face’: COVID-19’s long-term impacts
The group of long hauler patients is not limited solely to older individuals or people with pre-existing conditions.
Long-term symptoms from COVID-19 are hitting a diverse swathe of the population, including young people, according to El-Chemali.
“This is still very perplexing," the Mass. General doctor said. "We don’t know why this is happening.”
This is phenomenon is a concern for Nathan as well. He is worried about young people who are likely not going to die from the virus, but who may become debilitatingly sickened by it and then go on to suffer long-term symptoms.
“As the former surgeon general, if I see a lot of young, healthy service members get COVID, I know, fortunately, that their chance of succumbing to it is very, very, very low,” he said. “But in the back of my mind, I’m worried, OK, are there going to be any long-term residual effects in their body?”
At Mass. General, El-Chemali is noticing people who were fit and active before contracting the virus, young and old alike, who are all falling victim to months-long complications from the virus. The majority of these patients were not even hospitalized when they caught the viral respiratory infection, she noted.
These long haulers are not the same people as they were before they caught coronavirus, according to El-Chemali.
“Most of the patients we see were very functional," she said. “We’re seeing people who are health care workers, lawyers, people running companies, and clearly they are not able to do everything they were able to do before they got sick.”
As a doctor specializing in neuropsychology, El-Chemali is mainly studying people who have specific brain complaints as a result of coronavirus. Some have trouble remembering words. Others are suffering through extreme sluggishness.
The coronavirus survivors El-Chemali is tracking “cannot think straight," she bluntly stated.
These individuals are unable find words that would ordinarily come to them fairly easily, and they are experiencing “complete fatigue activity,” sitting on the couch for long periods at a time, even if they are usually active people, according to the doctor.
“The fatigue can be very debilitating," the doctor said. “They may be able to do something for an hour and an hour and a half, and then they need to sleep, relax.”
Other long hauler patients, El-Chemali said, are experiencing months-long lung complications from the virus, which, to some degree, is expected. Another percentage is having blood pressure and heart rate issues.
Earlier on in the pandemic, recovered COVID-19 patients' concerns about continued symptoms may have not been immediately validated, with doctors telling them that their symptoms would be only short-term. However, physicians are now seeing that that is not the case, El-Chemali said.
“It’s kind of like a slap in the face," she said of the continued symptoms.
Nathan explained that at a microscopic level, the virus is tearing up people’s lung cells, causing inflammation that may in turn create scar tissue and fibrosis. Patients are left with impaired lung activity that impacts their ability to exercise and undergo other straining activities.
"That’s bad in the lungs,” he said. “That’s what smoking does to people and other things is it creates this fibrosis and scarring and this damage to the lungs that are these spongey areas that, if they get damaged, may not recover.”
The immediate lung impairment COVID-19 patients are experiencing is not unusual, though. People who catch pneumonia and even a serious case of annual influenza may also see these bodily damages.
What is atypical is the long-lasting impact of the virus. According to El-Chemali, the SARS coronavirus of the early 2000s similarly caused continued symptoms, but with other more regular viruses, this is not the case.
The effects of the flu typically last only a couple days, El-Chemal explained. Patients may be a bit fatigued, but they get over it and do not have lingering symptoms.
With the coronavirus, however, patients can do well for several weeks before seeing symptoms return, both El-Chemal and Nathan pointed out.
“The concern from COVID is that unlike a case of garden-variety, if there is such a thing, pneumonia that people recover from and three months later feel fit as a fiddle, in COVID, they’re seeing that up to 50% of people who have had these serious illnesses can have long-lasting effects," Nathan said.
Wading through uncharted waters
Why some COVID-19 patients get the virus and remain completely asymptomatic while others become debilitated for weeks, even months, is the "million-dollar question, Nathan said.
Age, preexisting conditions and other factors certainly play a part, he said. But there are still a good number of unanswered questions.
“For the same reason that some people really just get swamped by this - because of age, lack of the immune system to really pull together, preexisting things - that’s going to create a total-body inflammation," the doctor pointed out.
Nathan compared the unknowns associated with coronavirus long haulers to victims of traumatic brain injuries.
When he served as surgeon general of the U.S. Navy, Nathan saw service members who suffered serious injuries from the blasts of IEDs and had their brains rocked, he said.
However, not everyone had the same medical reaction to the same explosion, the doctor noted.
Multiple service members may have been exposed to a single explosion. One might have walked away from the blast and suffered no health consequences, while the other may have been dealt a traumatic brain injury that caused decreased cognition, mental health issues and chronic headaches
The phenomenon left Nathan and other medical professionals full of questions about the discrepancy.
“We knew that at the cellular level, one’s brain cells were being severely affected and not so much in the other,” Nathan said. “We were racking our brains trying to figure it out.”
Similarly, medical professionals do not yet know why some COVID-19 patients' lungs cells are “exquisitely sensitive” to the virus and become severely inflamed while others remain perfectly healthy, Matthew said.
Long haulers' continued symptoms, particularly in relation to the brain, are “very startling,” El-Chemali added.
“We don’t really know what does this. We don’t know if this is the immune system driving this,” she said. “We know from autopsy results the virus doesn’t go to the brain. But there must be something giving people this post-viral syndrome.”
To answer some of her lingering questions, El-Chemali is helping lead a clinical research study with the Spaulding Research Institute in Boston, observing long haulers who contracted coronavirus and did not go to an intensive care unit but still wound up with long-term symptoms.
Although the study just recently started, dozens of people have already enrolled, according to El-Chemali.
Those running the study, like El-Chemali, hope to find out whether people who contract COVID-19 are more at risk of “brain trouble” down the line, she said.
“We are looking for commonalities. We’re looking for why they’re there and why they happen,” the doctor said. “Over time, what is happening with the brain with that initial COVID-19 insult? There is a very high possibility that it’s not just a one-hit and then business as usual.”
Linking radiation to coronavirus to help ‘long haulers’
One of Nathan’s main areas of interest is cancer and the effects of radiation, subjects that may, oddly enough, have a closer link to coronavirus long haulers than one might think.
The former U.S. Navy surgeon general previously advised the Minnesota-based pharmaceutical company Humanetics Corporation on the development of a medication that has shown to have positive results in thwarting the negative impacts radiation therapy has on the lungs of cancer patients.
The medication, called BIO 300, looked “very promising,” Nathan noted.
The drug was initially discovered by researchers at the United States Department of Defense in their efforts to create radio-protective drugs for the military, Humanetics said. The pharmaceutical company further expanded applications for the drug into radiation therapy.
Now, it may prove useful among COVID-19 long haulers in curbing the virus’s long-term side effects on the lungs.
While working with the federal government to develop the drug and make it available to the general public, Humanetics scientists compared notes with medical professionals caring for coronavirus patients and found the lung inflammation resulting from viral respiratory infection was similar to the lung injury caused by radiation therapy, according to Nathan.
“BIO 300 has been shown to mitigate inflammation of the lungs and pulmonary fibrosis caused by radiation,” Humanetics said. “It is believed that the same effect can be shown in COVID-19 patients.”
In July, the pharmaceutical company announced it received funding from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, to study BIO 300′s impact on coronavirus patients.
The study focuses on severe patients, many of whom were discharged from the hospital, were recuperating at home and may face the possible risk that their respiratory complications will continue to progress, leading to long-term lung function impairment, Humanetics said in a statement.
The study will be conducted by physicians at NYU Langone Health, located in New York Center, long one of the epicenters of the pandemic, Nathan noted.
The hospital system has treated over 10,000 coronavirus patients, and Dr. Rany Condos, who is leading the study, set up a post-COVID-19 recovery clinic and patient registry, Humanetics said.
As part of the study, NYU Langone plans to follow patients for a year to better understand the effects of recovering from coronavirus. Participants will give themselves BIO 300 daily for 12 weeks after being discharged from the hospital.
Researchers will then compare the lung function, exercise capacity and quality of life in the COVID-19 survivors who receive the drug against those who are given a placebo, according to Humanetics.
“This medication may block the same inflammatory process from COVID as it does in patients experiencing radiation therapy,” Nathan said. “It’s going to be important to find out one way or another, but regardless, these are the kind of studies that are needed.”