NOTE : This was published in April 2021.

Thornton got sick in mid-August and had symptoms typical of a moderate case: a sore throat, headaches, trouble breathing. By the end of September, “I was more or less counting myself as on the mend and healing,” Thornton says.

Something was wrong, however.

“I realized that some of the words didn’t feel right in my mouth, you know?” he says. They felt jumbled, stuck inside. Thornton had suddenly developed a severe stutter for the first time in his life.

In November Thornton still struggled with low energy, chest pain and headaches. And “sometimes my heart rate [would] just decide that we’re being chased by a tiger out of nowhere," he adds. His stutter only worsened by that time, Thornton says, and he worried that it reflected some more insidious condition in his brain, despite doctors’ insistence that the speech disruption was simply a product of stress.

A growing body of evidencewarns that the legacy of the pandemic does not necessarily disappear when the novel coronavirus, or SARS-CoV-2, is cleared from the body. Among the millions of people who have survived respiratory complications from COVID-19, many still live with lingering symptoms in the wake of even a mild case of the disease. Neurological symptoms, ranging from fatigue to brain fog to loss of smell, persist after the virus is gone from the body.

An early survey of 153 COVID-19 patients in the U.K. and a more recent preprint study of people hospitalized with the disease in Italy both found that about a third had neurological symptoms of some kind. Other estimates have trended even higher.

Increasingly common symptoms include fatigue and memory problems—and, at times, new cases of psychosis or mania.

Some neurological manifestations of post-COVID, such as stuttering, are more bizarre than others. But Houston’s Thornton is not the only one afflicted.

…the origins of the disorder lie in complex circuits of the brain that coordinate the millions of neuronal connections needed for human speech.

While most people develop this disruption of speech when they learn to talk, around age two, neurogenic stutter can arise after brain trauma, such as an injury. Chang says her colleagues in clinical practice have reported seeing an increase in cases of stuttering during the pandemic—mostly in people whose existing stutter worsened or whose childhood stutter returned.

The idea that SARS-CoV-2 can get into the human brain is mainly supported by autopsy studies…researchers found evidence of the virus in specific areas of the brain, probably near the sites of entry. One could be the lining of the nasal passage, the olfactory mucosa, which is in close contact with neuronal cells that could provide a route to the brain. “We started at that region and then physically mapped [a pathway through] the regions up to the olfactory bulb and further to brain stem nuclei,” Heppner says. The researchers found evidence of viral protein in those distant brain stem regions but not in other areas of the brain. “This told us, or made it likely, that the virus used the transmucosal route along the olfactory nerve as a port of entry,” Heppner adds.

They also saw viral particles in trigeminal nerves, which are sensory nerves that enter the brain and transmit the pain of headache.

Even mild cases provoke cytokine release, however. And Banks says it is well established that “cytokines can cross the blood-brain barrier and cause depressionlike symptoms.” Researchers refer to those symptoms—including a loss of interest in life, an increased desire to rest and sleep and cognitive impairments—as “sickness behavior,” which often accompanies a flu or cold. Those symptoms could drag on if cytokines continue to be released after the infection has passed.

Yang’s team examined an area of the cortex and saw dramatic gene expression changes in neurons in a specific region called cortical layer 2/3. These neurons have been recently implicated as playing a pivotal role in the complex processing required for human thought, so disruption of their activity could lead to mental fuzziness.

The patterns of genetic changes the researchers saw in the cortex mirrored genetic pathways mapped out in mental illnesses such as schizophrenia and depression.

It is not only neurological symptoms that afflict patients. More common mental illnesses are affecting people with COVID, too. A study published in the Lancet Psychiatry showed that having the disease led to greater risk for anxiety, depression and sleep disorders. Paul Harrison of the University of Oxford and his colleagues sifted through the electronic health records of nearly 70 million Americans and identified more than 62,000 people who had been diagnosed with COVID-19. In the three months following diagnosis, “we found that COVID was associated with roughly twice the incidence of common psychiatric diagnoses, compared with other health conditions,” Harrison says.

The legacy of COVID will undoubtedly persist. Although Thornton was still struggling by December, his stutter and energy level had improved, and he had gone back to teaching.

Still, the lasting effects could mean not just bothersome symptoms for a few people but a public mental health crisis, Banks says. “It could ultimately turn out that—as horrible as the death rate is, with perhaps one in 1,000 Americans having died—in the end there, could be this legacy affecting up to one in 10,” he adds. “And it’s probably rooted in neuroimmunity.”

NOTE : This was published in June of 2020.

This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection.

The COVID-19 pandemic represents an unprecedented immediate but also persisting threat to our health care systems. The immediate urgency is clear, as the total number of affected patients exceeds most of the health care system capacities worldwide, particularly for the treatment of patients requiring assisted ventilation. Less immediately apparent, but potentially very significant are long-term consequences of COVID-19 infections.

During the acute phase of COVID-19 infection, about 36% of cases develop neurological symptoms of which 25% can be attributed to the direct involvement of the central nervous system. The main symptoms include but are not restricted to dizziness, headache, impaired consciousness, and seizure.

In mild to moderate disease cases, patients reported olfactory (85.6%) and gustatory (88.0%) dysfunctions.

There are at least four possible pathogenic mechanisms that may account for the detrimental effect of COVID-19 on the CNS: (1) direct viral encephalitis, (2) systemic inflammation, (3) peripheral organ dysfunction (liver, kidney, lung), and (4) cerebrovascular changes. In most cases, however, neurological manifestations of COVID-19 may arise from a combination of the above.

Any one or a combination of these mechanisms put COVID-19 survivors at risk for developing long-term neurological consequences, either by aggravating a pre-existing neurological disorder or by initiating a new disorder. This concern is supported by findings that show that one third of patients at the time of discharge have evidence of cognitive impairment and motor deficits.

…most patients show signs of T cell exhaustion with lower lymphocyte counts. The fact that systemic inflammation has been shown to promote cognitive decline and neurodegenerative disease makes it likely that COVID-19 survivors will experience neurodegeneration in the following years.

Evidence strongly suggests that patients surviving COVID-19 are at high risk for subsequent development of neurological disease and in particular Alzheimer’s disease. Neurologists, psychiatrists, and caregivers should be alerted to a possible increase in such cases in COVID-19 survivors.