How long will covid reshape the brain – and how we might treat it

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The young man pulled something from behind his two ears. “I can’t hear anything without my new hearing aids,” said the 32-year-old husband and father. “My body is broken, Doc.” A former firefighter and emergency medical technician, he had had covid more than 18 months previously and was nearly deaf. He also recently suffered from crippling anxiety, cognitive impairment and depression. Similarly, a 51-year-old woman told me in tears, “It’s been almost two years. My old self is gone. I can’t even think clearly enough to keep my finances straight. They are real people immersed in the global public health catastrophe of the long covid, which the medical world is struggling to grasp and society is struggling to cope with.

As such stories make clear, covid is biologically dangerous long after the initial viral infection. One of the main assumptions behind the long covid is that the coronavirus is somehow able to establish a reservoir in tissues such as the gastrointestinal tract. I believe the long covid explanation is more sinister.

Science is showing more and more clearly that covid-19 activates inflammation and impairs the nervous system even when the virus itself appears to be long gone. The virus begins by infecting cells in the nasal and respiratory lining, and the resulting inflammation sends molecules into the bloodstream that trigger the release of cytokines in the brain. This can happen even in mild cases of covid. Through these cell-to-cell conversations, cells of the nervous system called microglia and astrocytes are accelerated in such a way that they continue for months or even years. It’s like a stone weighing down the accelerator of a car and causing the engine to spin uncontrollably. All of this causes damage to many cells, including neurons. It is high time that we recognize this fact and start integrating it into the way we care for those who have survived covid.

For too long, the mysteries of the long covid have led many medical professionals to dismiss it as an incurable disease or a psychosomatic disease without scientific basis. Part of this confusion comes down to the jerky pace of scientific progress. Early in the pandemic, autopsy results from patients who died of covid “did not show encephalitis or other specific brain changes related to the virus,” as one report noted. Patients with deep neurological diseases resulting from covid-19 had no trace of the virus in the cerebrospinal fluid wrapping their brains.

These studies left most medical professionals mistakenly convinced that the virus was not damaging the brain. Accordingly, we focused on the lungs and heart, then scratched our heads in wonder at the coma and delirium found in over 80% of covid ICU patients. A robust study from the Netherlands showed that at least 12.5% ​​of covid patients end up with long covid three months later, but because ‘brain fog’ was not identified until later in the pandemic, these researchers did not include cognitive or mental problems. health conditions in the data they collected. So this otherwise beautifully executed study almost certainly underestimated the rate of long covid.

Since the early days of the pandemic, we have learned a great deal about the neurological effects of SARS-CoV-2. Earlier this year, the UK Biobank’s neuroimaging study showed that even mild covid can cause an overall reduction in brain size, with noticeable effects on the frontal cortex and limbic system. These findings help explain the deep anxiety, depression, memory loss and cognitive impairment experienced by so many long-time patients.

A new study published in the Lancet of more than 2.5 million people compared covid-19 patients with non-covid patients to determine the rate of recovery from mental health problems and neurological deficits like depression and brain fog in my own patients. What he revealed is partly encouraging and partly devastating: anxiety and mood disorders in long covid tend to resolve over months, while severe dementia-like issues, psychosis and seizures persist at two years.

Now researchers are putting the science together to piece together what happens at the cellular level with long covid, using animal models. As in the lungs, blood vessels in the mammalian brain are lined with endothelial cells, which have receptors for angiotensin-converting enzyme 2 (ACE2), a protein to which the coronavirus “clings”. Once infected, these cells become inflamed, leading to problems with blood flow and loss of integrity in the brain’s protective fortress, the blood-brain barrier. When this barrier is damaged, inflammatory cells and fluid leakage trigger a process of swelling and brain damage that can be difficult to stop. The hamsters and mice in these studies don’t imagine the symptoms and tissue changes, and neither do our patients.

How to calculate risk in the age of long covid

Medical researchers recently learned that the coronavirus can also infect cells called astrocytes, the glue that holds the brain together. Instead of using the ACE2 receptor, it appears that SARS-CoV-2 attacks astrocytes via completely different types of glycoprotein receptors. When the virus directly damages astrocytes and other cells of the nervous system, the supportive and nurturing environment of our 100 billion neurons breaks down. Even though neurons are not directly infected, the brain’s intercellular relationships are so intimate that infecting other cell types creates a cascade of brain damage.

Corroborating evidence of brain dysfunction in long-term patients comes from abnormal PET scans that show ‘cold’ spots in the olfactory and limbic systems as well as the brainstem and cerebellum – as if these areas are changing from vibrant to withered . The way the brain machinery slows down aligns with patients’ problems with smell, memory, cognitive abilities, chronic pain and sleep disturbances.

Long-term patients face difficulties when trying to complete the tasks associated with their job. When we test them at Vanderbilt University’s Critical Illness, Brain Dysfunction, and Survivorship Center several months after their initial infection, they show profound memory deficits and executive dysfunction – problems completing daily tasks and to-do lists. , meeting schedules, emotional control, data analysis and information processing. In other words, they find it difficult to live their life. In fact, their symptoms are similar to those of mild to moderate Alzheimer’s disease, or the type of brain damage seen in cancer patients after chemotherapy and in intensive care survivors with post-intensive care syndrome. Clinically, there are also many overlaps between long covid-related brain fog and the cognitive dysfunction seen in patients with myalgic encephalomyelitis/chronic fatigue syndrome.

A long covid could change the way researchers study chronic diseases

The bad news is that this neurological injury occurs most often in young long covid patients (20-50 years old) who have never been hospitalized for covid. The good news is that, at least in some patients, it may not be permanent or progressive. Our clinical experience and clinical trials have shown that cancer patients and intensive care survivors with newly acquired dementia-like brain damage can become more mentally sharp after months of exercising their brains with computer programs as well as games. of words and numbers. We recently completed, in a paper in submission, a 10-year neuropsychological follow-up analysis of our large cohort study of ICU survivors and found that approximately one-third remain the same, one-third improves and a third suffers inexorably. decline.

First, we physicians need to validate the stories and complaints of our patients. They don’t invent anything. I often feel the need to apologize to my patients for not having enough answers and treatment options. Then I assure them that I will not leave them as we gain more knowledge and options to improve their health in the months and years to come.

Second, there is a need for well-designed, randomized, placebo-controlled clinical trials of drugs and other treatment approaches for patients with long covid. Too many people lose hope. A study of 150,000 covid survivors showed a 10 to 15 times higher risk of contemplating suicide compared to 11 million control patients. Many drugs are on offer and trials should target specific symptoms such as brain, heart or lung problems to make faster progress in specific areas.

Additionally, patients should be aware that the brain has an extremely powerful ability to reshape itself. Its 1,000 trillion synapses are constantly changing every second of every day. It is too early to know if this neuroplasticity can be exploited for long-term patients. But our lab at Vanderbilt and other researchers are studying whether computerized cognitive rehabilitation programs will help patients recover brain function.

Finally, a good dose of compassion and empathy will help start the healing process for those who feel alone in the haunted house of their own body, lighting a candle towards healing.

About Margie Peters

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