Understanding The Neurological And Psychological Effects Of Covid-19

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More than a year into the Covid-19 pandemic, the subject of “long Covid,” the symptoms of the disease that go on for weeks or months, is gaining in prominence and importance. Of particular interest are the neurological and psychological complications that can linger on in Covid-19 survivors long after they’ve left the hospital and returned to their homes.

Reports of long-term fatigue, “brain fog,” and post-traumatic stress disorder are increasing in number, but still lacking in clarity as far as underlying mechanisms are concerned. Some of these neuropsychiatric effects, like the loss of taste and smell, are transient, appearing as the disease progresses and subsiding once the virus clears. But others are more persistent—and potentially, even lifelong, like damage from stroke. 

Though neurological and psychological complications can be collapsed into one category, the more evidence that emerges, the more imperative it becomes, for the purposes of care and treatment, to distinguish between the two. Neurological symptoms pertain specifically to damage the virus causes, whether directly or indirectly, to the nervous system, while psychological symptoms encompass behavioral, emotional, and cognitive impairments.

Neurological Covid-19 symptoms in particular have been difficult to round up and pin down due to their variability. Milder forms include fatigue, headaches, and the now infamous loss of taste and smell, while severe symptoms range from strokes and seizures to encephalopathy (brain disease), encephalitis (brain inflammation). And it may happen rarely, but some Covid-19 patients develop either an autoimmune condition known as Guillain–Barré syndrome (GBS) or acute transverse myelitis—inflammation of the spinal cord. About two percent of patients experience ischemic stroke, which occurs when clotting blocks the flow of blood to the brain.

Psychological complications, on the other hand, are not just wide-ranging, but more ubiquitous. It is common for patients who end up in the ICU—those with severe Covid-19 certainly, but other emergencies as well—to at some point experience delirium due to the acute stress of invasive procedures like surgery and intubation. Many who leave the hospital after being treated for critical illness go on to develop post traumatic stress disorder (PTSD). Even Covid-19 survivors who only had mild cases of the disease might struggle with “brain fog,” the term attributed to the muddledness in memory and mental clarity that can linger on months after the virus has cleared.

We can’t say for sure how SARS-CoV-2 causes neuropsychiatric complications in those it infects. But the presence of certain neurological symptoms has also been linked to a greater risk of either longer hospital stays or in-hospital mortality. The risk of death for hospitalized patients who develop toxic metabolic encephalopathy, for example, is 24 percent higher, according to a recent study completed by researchers at NYU. In other words, these symptoms signal a need for more intensive care, even if they’re not accompanied by the more recognizable signs of distress, like breathing difficulties.

What is certain is that strokes big and small could either damage the brain permanently, or create blood clots that resolve over time and induce brain fog. The vascular systems of critically ill Covid-19 patients also produce a wide variety of inflammatory cytokines—the namesake of the cytokine storm, an immune reaction capable of sending the body into hyperdrive and inducing damage so pervasive, it reaches the brain. Our brains are so vascularized that tiny blood vessels known as capillaries surround almost every single neuron. If these capillaries are made leaky and more permeable by extensive inflammation and clotting, that could leave the door open for extensive neurological damage. 

One of the biggest questions up for debate is whether or not SARS-CoV-2, the virus that causes Covid-19, can directly enter and infect the brain. Its ability to do so depends on the presence of ACE2 receptors in our neurons—the most fundamental unit of the nervous system—and our astrocytes, star-shaped cells that populate the brain and spinal cord and serve many protective and communicative functions. Some researchers have observed ACE2 expression in laboratory-grown cell cultures and deemed this enough evidence to substantiate the hypothesis of direct infection. But at least one brain autopsy report, compiled by neuropathologists at Columbia University, ruled against the possibility when no virus was detected in the brains of 41 patients who lost their lives to Covid-19 during their respective hospitalizations. 

More studies that distinguish between neurological and psychological symptoms but examine them in conjunction are needed for us to understand how they coalesce and interact. One of the largest studies to examine both, a retrospective assessment published in The Lancet earlier this month, pooled the health outcomes of almost 240,000 Covid-19 patients—reported over a period of six months—and cross-analyzed them with survivors of other respiratory infections. Compared to the flu, the researchers found their subjects were 44 percent more likely to develop neurological or psychiatric complications. Most of these patients had mental health conditions like depression or anxiety, while those with severe illness experienced a greater share of dementia and stroke.

As the NYU study, reflecting the opinions of Dr. Steven Galetta, makes clear, it can be difficult to distinguish between the long-term neuropsychiatric effects normally seen in patients who have spent extended periods of time intubated or in intensive care. In any case, the effects Covid-19 has on the brain are too apparent to be negligible, even if we don’t know exactly why or how they manifest. Physicians caring for Covid-19 patients must allow the evidence amassed so far to inform their clinical practices and recommendations for care. Significantly more research is also needed to understand how neuropsychiatric Covid-19 symptoms work and how to treat them. Last but not least, those of us lucky enough to have evaded Covid-19 infection must take note and take caution as more infectious variants of SARS-CoV-2 spread far and wide. This virus only continues to surprise us with its capabilities—no need to learn about them the hard way.

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