PracticeUpdate: You were instrumental in identifying the neurological symptoms of COVID-19 when the virus first appeared. What have we learned about the neurologic manifestations of this disease?
Dr. Nath: Neurological complications were not initially recognized. People thought it's a respiratory illness, and that happens quite often in most epidemics and pandemics. People get focused on the initial manifestations of the infection, and they only realize much later in the course that the brain gets involved. But, in fact, in almost all these infections, whether it's Zika or Dengue or Ebola or HIV, they all affect the brain. The same is true of coronaviruses. They're thought to be respiratory viruses, but they have profound effects on the brain, and people didn't realize it until much later.
It has now become clear that there are two types of manifestations that occur. Broadly, there are two types of manifestations. One is during the acute phase of the illness, and the other is what we call post-viral syndromes. If you look at patients who are hospitalized with coronavirus, about one-third of them complain of encephalopathy, and their hospital stay is two or three times longer than those that do not have neurological complications. Two-thirds of them upon discharge cannot take care of themselves. The effects are quite profound. They can also develop strokes, seizures. They can get encephalitis, which can be an immune-mediated encephalitis. Rarely they can get viral encephalitis. They can get peripheral neuropathies, they can get myelitis, and they can get Guillian-Barre syndrome.
There are a number of these complications that can occur in the acute phase, and some of these immune-mediated ones can occur in the post-viral phase. That means when the virus cannot be detected as being replicating, they can develop immune-mediated phenomenon within the brain, spinal cord and the peripheral nerve and muscle, much later in the course of the illness. Some patients can develop a myositis. It can be the skeletal muscles or even involve the cardiac tissue.
Strokes are quite interesting in these patients. Some of them can be immune-mediated: they get a hypercoagulability and that hypercoagulable state can lead to occlusion of multiple arteries and veins at the same time. Some patients will develop hemorrhages. They can develop micro hemorrhages throughout the brain, and that is because the virus tends to invade the endothelial cells, and by doing so you can disrupt the blood-brain barrier, and blood will leak into the parenchyma in that way.
There are other long-term complications that patients have started complaining about, and those overlap with what we call myalgic encephalomyelitis, or chronic fatigue syndrome. A number of these patients had minor symptoms with COVID. They did not necessarily get admitted to the hospital. They were able to manage things themselves, and they've felt that they've recovered. However, they continue to complain of difficulty sleeping at night. They have extreme exercise intolerance, difficulty concentrating, which they term mental fog. They have tachycardia upon standing or upon minimal exercise. They feel palpitations. They can have sweating abnormalities or powerful vasoconstriction. So, there a lot of autonomic symptoms associated with this illness, as well. These patients have been calling themselves long-haul COVID, and the pathophysiology of this is very poorly understood. We are very eager to study these patients here at NIH.
PracticeUpdate: Based on the preliminary data that you have for some of these serious adverse effects, whether it's cerebrovascular adverse effects or Guillian-Barre or the chronic fatigue syndrome scenarios, do we know if standard treatments are effective? Have you seen anything anecdotally that you would like to pass on to our viewers?
Dr. Nath: There are treatment guidelines that have already been established by a number of agencies, and they are widely available. Management of stroke and prevention of stroke in COVID patients has been a very hot topic. The recommendations are to monitor these patients for D-dimer levels and treat them with anticoagulants if they're hospitalized, and then they need prolonged treatment for some period of time even after they're discharged. A number of patients may even have underlying risk factors for a stroke or coronary artery disease. Those patients need to be treated for all those aspects as well. That cannot be ignored. Then there are treatment guidelines that are being established for patients with seizures or who used to have seizures and now have COVID. Those are worth taking a look at.
With regards to the long haul COVID or ME/CFS-type symptoms, that remains a challenge. I think once these patients come with long-term complications, we need to make sure that there is no underlying explanation for it. The first thing is to make sure there isn't a underlying thyroid disease or kidney disease or something that may have gotten unmasked and that the patient wasn't aware of that could be a treatable entity. Then if none of that is there, they can still be managed symptomatically. For palpitations one can use beta blockers, and they can be used safely. If there's postural hypertension, then that can be treated. So there are a number of symptomatic things that can be done, but it is also important for us to try and determine the underlying pathophysiology of the disease, so some of these patients should be enrolled into clinical trials that are ongoing or are being put together. That's an excellent opportunity to try and understand the basis or new treatments for them.
PracticeUpdate: For the non-neurologist who may be the primary treating physician for a patient with COVID, are there any tips or suggestions that you would like to offer or any recommendations as to when they should immediately seek a neurologic consult?
Dr. Nath: These patients are complicated. If the patient has common neurological manifestation and is complaining of headaches, they should be treated just like you would treat any other patient, right? But if they're developing Guillian-Barre syndrome, those need to get neurologists involved early on in the care of these patients. They can help guide you on the treatment of these patients, but other symptomatic treatments should be provided to this patient just as one would do for the non-COVID patients.