Long-Term Effects of COVID-19

“I was a healthy, active person with no health problems,” Jenifer Johnston told ABC News affiliate KATU, in Portland, Ore. “I was happy, and now I can barely walk.” Johnston contracted the SARs-CoV-2 virus in March 2020. A year later, she is adjusting to life with long COVID, or “long-haul” COVID-19 symptoms as some in healthcare phrase it. Even now, she suffers from shortness of breath, lack of endurance and cognitive issues such as severe short-term memory loss and anxiety that were not present prior to her illness.¹ Unfortunately, she is far from alone.  

Perhaps you have seen patients such as Johnston at your own healthcare facility. Or, perhaps you have seen them unknowingly, unaware their symptoms are actually COVID-19-related, occurring weeks and months after their recovery from the initial COVID-19 infection. 

Regrettably, few physicians are yet aware that long-haul symptoms can occur even months after the infection, and the long-term problems such as brain fog and fatigue are often misdiagnosed or even dismissed. Pediatric nurse Jennifer Minhas, another COVID-19 survivor, is one example of this. Last year, she experienced new symptoms, including severe fatigue, heart palpitations and chest pain, four weeks after she had recovered from the initial illness. When she sought help medical help for the issues, her primary care physician told her she was just being overly anxious. According to Minhas, “That wasn’t what I needed to hear.”² 

In fact, it is not what any “long-hauler” needs to hear. Somewhere between 10 percent and 30 percent of COVID-19 sufferers experience long-term side effects (the actual percentage is unknown since the illness is still relatively new and data are still being gathered). After months of being labeled “long COVID,” in February, Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, revealed its new official name: post-acute sequelae of SARS-CoV-2 (PASC) infection.³ PASC symptoms can include chest pain, heart palpitations, orthostatic intolerance, crushing fatigue, brain fog, anxiety, inability to concentrate, lingering cough, lack of endurance, memory problems, depression and many others since the list of reported symptoms is vast, complex and seemingly ever-growing. 

Observations from the Johns Hopkins COVID Clinic

PASC clinics are being launched around the United States to help COVID-19 patients cope with the aftermath of this vicious illness. The Johns Hopkins School of Medicine’s Post-Acute COVID-19 Team (JH PACT) is one of, if not the most well-established, such clinics. It is perhaps the longest running in the country, having opened its doors in April 2020, when doctors first recognized the need for a multidisciplinary, collaborative, ambulatory framework that supports COVID-19 survivors. 

Alba Azola, MD, a physical medicine and rehabilitation specialist, assistant professor at the Johns Hopkins School of Medicine and co-director of the PACT clinic, says, “We knew from work in our institution that patients who have prolonged intensive care unit (ICU) stays present with post-intensive care syndrome, affecting mental health and causing cognitive as well as physical impairments, including chronic fatigue, nerve damage, critical illness myopathy, anxiety, depression, post-traumatic stress disorder, and  impaired attention and memory. Because of the pandemic, we realized we were going to have an influx of patients who were going to have prolonged hospital stays who were going to need pulmonary, as well as rehabilitative care. So with that in mind, we decided to start creating a system to provide the needed services. That’s how our PACT clinic came about.”

And doctors at JH PACT soon noticed something unexpected. “We quickly started seeing that not only patients who had ICU stays had long-term symptoms,” Dr. Azola says, “but we also started seeing that patients who did not require hospitalization also presented with long-term, lingering symptoms. Then, the clinic started seeing both types of patients. In terms of the symptoms, they present a little differently. In the cases that had a severe COVID 19 [illness] with prolonged mechanical ventilation, they will present with severe deconditioning and muscle weakness, in part from requiring paralyzation for venting and being bedbound for weeks. In this population, we usually start the rehabilitation in the ICU, and some may require subsequent admission to an inpatient rehabilitation unit. Once we see them [as an] outpatient, we continue to progress them with outpatient physical, occupational and speech therapy to continue to recover endurance and build strength. A lot of them present with cognitive impairment — mainly memory deficits, deficits in concentration and brain fog. There’s another group of patients, and these are the patients who did not stay in the hospital who also present with chronic fatigue, palpitations, deconditioning and quite a bit of cognitive impairment when it comes to memory and higher-level cognitive tasks. They also present with difficulty in tolerating changes in position or posture, or postural orthostatic tachycardia syndrome (POTS)-like symptoms.”

Tae Chung, MD, a physical medicine and rehabilitation specialist and an assistant professor of physical medicine and rehabilitation and neurology at the Johns Hopkins University School of Medicine, is founder of the POTS clinic at Johns Hopkins. He says POTS is largely misunderstood in general, and now that many long-hauler COVID sufferers are displaying POTS-like symptoms — or “COVID POTS” — he wants to raise awareness about this disorder. Dr. Chung says he sees many long-haulers present with “a lot of severe fatigue and brain fog, which are very typical symptoms of POTS. And though there is no official data or solid research just yet, surveys and several publications indicate that more than 90 percent of COVID long-haulers were either asymptomatic or had very mild infections of COVID-19. These are not patients who were in the ICU.” He also expects to see many more such patients, which he adds, “is truly scary.”

“POTS is a true neurological disorder, though many doctors do not recognize it and even dismiss it,” he says. “It takes, on average, six years for a patient to be diagnosed with POTS, even though POTS is one of the most typical reasons for chronic fatigue and brain fog, which are so common today.” And as for how POTS might play a role in COVID-19, Dr. Chung says, “I see a large number of patients who present with POTS-like symptoms in the clinic now because of COVID-19. There is good evidence that POTS is basically a sympathetic neuropathy of denervation. And that denervation affects blood volume, among other things, causing dizziness, fainting, chronic fatigue and brain fog, all of which are seen in typical POTS and COVID POTS. Though there is not yet research to back this theory up, what I have observed makes me wonder whether there is something very specific about the virus that causes COVID-19, since I have never seen this many patients come in with POTS-like symptoms after having the flu, for example. The COVID-19 virus seems to directly infect the sympathetic nerves, which causes blood vessels to contract differently, negatively affecting blood regulation and leading to COVID POTS.”

Nisha Gilotra, MD, assistant professor of medicine at the Johns Hopkins School of Medicine in the division of cardiology, echoes Dr. Chung’s observation with regard to COVID’s ability to directly infect tissues and damage blood vessels, adding her own perspective on heart involvement. “We are learning more and more every day in terms of how the virus responsible for COVID-19 can affect the heart,” she explains. “There is much more to it than its ability to affect the respiratory system. It can actually enter the cells in the heart directly and affect the heart in a multitude of ways. In the acute setting, because of the systemic inflammation, it can cause an inflammatory cardiomyopathy or something called myocarditis, a condition garnering a lot of attention in the media and in scientific studies. We’re learning that myocarditis is probably less commonly occurring than we think, and that this virus has the ability to actually affect the blood vessels more so in the heart, like it does in the rest of the body, and cause damage to the heart that way by disrupting the surface of the blood vessels. This can lead to a number of different things clinically, with one of them being blood clots.”

“For patients who have had COVID-19, who don’t have a cardiac history,” Dr. Gilotra adds, “my colleagues and I are seeing long-hauler syndrome or long COVID syndrome, where the symptoms can often be nonspecific. They can cover a lot of organ systems, and present with fatigue, shortness of breath, palpitations and dizziness, among other manifestations. It could be the respiratory system, the cardiovascular system or neurologic. And so, what’s been important for us, my colleagues and I, is to really have a multidisciplinary approach to patients so that we’re taking all of the organ systems into account. We’re also trying to recognize when it would be appropriate to do further evaluation from a cardiac perspective. There is more and more data coming out of MRI and other imaging studies where, in patients who otherwise don’t have cardiac issues, the rate of cardiac involvement in a minor infection is very, very low, so keeping that in mind.” 

Post-COVID Syndrome?

No one expected post-polio syndrome to afflict polio sufferers many decades after they contracted and survived the polio virus. Is it possible a post-COVID syndrome could attack in a somewhat similar manner, even if PASC abated decades prior? “That’s the big question,” Dr. Azola explains. “That is something that we, by following the patients, researching the natural history of their disease and getting a biorepository of samples, we can identify different biomarkers that could help us understand what patient factors, as well as viral factors, are affecting the people who have long-term symptoms. We are meeting with a group of infectious disease doctors who started very early with intervention for outpatients, or patients who were never hospitalized but sought treatment for COVID, whether it was convalescent plasma or monoclonal antibody. These specialists want to collaborate with us to help look at that population to see how treatments can impact it as well. So there’s a lot of work to be done, and we don’t have the answers right now, but we are trying to come up with the questions and find ways to make better-informed decisions and better counsel patients.”

What Else Should Physicians Know?

Soo-Yeon Kim, MD, a physiatrist, director of musculoskeletal medicine in the Johns Hopkins Musculoskeletal Center and co-director for the PACT clinic, explains how important it is for primary care physicians and other healthcare professionals to understand patients do suffer symptoms even months after COVID-19, even if they were initially asymptomatic. “It’s real, and awareness is really important,” she says, explaining Johns Hopkins has seen many long-haul COVID patients arrive at PACT from other healthcare facilities because their primary care physician or other doctors did not believe them regarding long-term symptoms. They were dismissed and sometimes even belittled. “Healthcare providers should be aware of the long-haul symptoms and find resources around their region to help their patients,” she explains. “Many primary care physicians are not really familiar with these types of symptoms, and at times they mismanage them or think that the patient is normal when they are not. This leads patients to experience more anxiety and depression, thinking that they are crazy. But when patients present with cognitive symptoms and mental health issues months later, don’t assume that they are crazy. Just because their labs and studies might be normal, these patients are telling the truth, and they are genuinely suffering. We just don’t know the exact mechanism of COVID-19 yet, but don’t underestimate the effects of COVID. Initially, when ICU patients are discharged, they are so happy that they survived, but they don’t realize the long-term effects of it. And months later, they’re learning their judgment and memory are not as good as before, which is very discouraging.” 

Dr. Azola is just as passionate about telling physicians and other healthcare workers that long COVID is real. “A lot of patients find that some healthcare providers don’t necessarily believe what the patient is feeling or experiencing,” she says, “and it can be debilitating to the point where they have physical difficulty going back to work, for example. And it can be difficult for them to find providers who understand that these are real side effects of having the infection. So, I think that it’s important to have an awareness that there are a significant group of patients who will continue to present long-term symptoms after the infection, and that there are ways we can support their recovery and help them recuperate and get back to their normal lives. I think providers should be aware and should be able to direct their patients to find the providers who are treating this, because there are ways that we can help them cope and help them compensate and get back to more normalcy. Anywhere they will let me speak, I will try to spread the word. This is a real collection of symptoms, and these patients need help.”

Dr. Kim also stresses the importance of physiatrists who work in the relatively underpublicized medical field of physical medicine and rehabilitation. “A lot of people think COVID-19 affects primarily the lungs, and it’s a respiratory disease,” Dr. Kim explains. “They all think that this is a medical condition, so they run labs and images and all that. Actually, what we’re seeing more is that after they recover from the infection, what long-haulers really need is functional recovery or cognitive recovery. And the people who are specialized in that are physiatrists. We are the ones who can manage all of the symptoms, and I think people will need more awareness of this field and [need to know] where to go to when those symptoms happen. Primary care physicians might not know this yet.”  

The Future

During 2020, medicine meant constant discovery for healthcare workers who fought to treat COVID-19 and learn more about its mechanisms and symptoms. The world, too, has been focused on keeping the virus at bay through masks, social distancing and handwashing, among other preventive measures. And a year into this process, medical professionals now know much more as data are multiplying and studies continue. 

What does the future hold for both long-haulers and COVID-19 research and treatment? Dr. Gilotra is hopeful. “I think that we are, as a profession, evolving our focus in the pandemic,” she says. “The last year has been dedicated to prevention and treating patients who are acutely ill, figuring out when to test patients, when to clear them, etc. But I think this next phase is really going to focus on the long-term consequences of COVID-19 infection, ranging from cardiovascular complications to respiratory, to psychosocial impacts. I think we’ve yet to learn a lot more about what the longer-term impact is going to be. We will advocate for the profession to dedicate efforts to this very important aspect of COVID-19.”

Indeed, now that long-term symptoms of COVID-19 have been identified as PASC, Dr. Fauci said the National Institutes of Health (NIH) had been granted $1.15 billion in funding over the course of four years to look at PASC, how it affects the population, and how many people have it. “It’s very difficult to treat something when you don’t know what the target of the treatment is,” said Dr. Fauci. “And, that’s the reason why it’s extremely important to take a look at these individuals, not only the scope of this and not only, you know, the depth and breadth of the symptoms, but also to try and have some correlate that actually is the pathophysiological correlate.”³