Persistent or prolonged COVID manifests itself with numerous symptoms that can persist for weeks, months, and even years after having overcome the coronavirus infection, and that are very varied and of different intensity in each patient, although many of those affected complain of mental or brain fog, which is used colloquially to refer to the presence of significant and persistent cognitive deficits, which are characterized by a continued impairment of executive functioning and working memory.
These people may experience a lack of mental clarity, problems with attention, concentration and memory, or difficulties in performing common tasks, among other disturbances. Now, scientists from the Yale School of Medicine (USA) have discovered a potential treatment to reduce these annoying and disabling symptoms. These researchers have tested two already available drugs in a group of people and preliminary tests reveal that if given together they can reduce or even eliminate brain fog, according to results published in Neuroimmunology Reports.
Guanfacine, developed in the lab of Amy Arnsten, Albert E. Kent Professor of Neuroscience and Professor of Psychology, was approved by the US Food and Drug Administration (FDA) for the treatment of ADHD in 2009, but doctors also they have used it for other prefrontal cortical disorders such as traumatic brain injury and post-traumatic stress disorder (PTSD). Arnsten has now collaborated with Dr. Arman Fesharaki-Zadeh, an assistant professor of psychiatry and neurology, who has long treated COVID-19 patients with a combination of guanfacine and N-acetylcysteine (NAC), an antioxidant that is also used to treat traumatic brain injury.
“There is a shortage of treatment for prolonged COVID brain fog and these drugs (guanfacine and N-acetylcysteine) are affordable and widely available”
This combination therapy was effective in relieving brain fog in their small cohort of patients. And while new placebo-controlled clinical trials with larger numbers of participants are needed to establish these drugs as an appropriate treatment for post-COVID-19 neurocognitive deficits, researchers have stated that they may be available to patients now if their doctors want to prescribe them.
“There is a shortage of treatment for prolonged COVID brain fog, so as I continued to see the benefits of this treatment in patients, I felt the urgency to spread this information,” Fesharaki-Zadeh said. “You don’t need to wait to be part of a research trial. You can ask your doctor – these drugs are affordable and widely available.” Because they have been approved by the FDA and have been in use for years, they are considered safe for patients.
Drugs that protect the brain against inflammation and stress
The prefrontal cortex of the brain is responsible for executive functioning and working memory, as well as regulating attention. Neural circuitry in this region is “remarkably vulnerable” to inflammation and stress, explained Arnsten, who has studied the circuitry underlying cognition for decades.
“The circuits that generate higher cognitive function have very special molecular needs because they have to create neural activity without any kind of sensory stimulation, for example, abstract thoughts and memories,” he says. “Neurons have to generate and maintain their own activity” and, according to this scientist, inflammatory factors can interfere with these molecular needs and inhibit the ability of circuits to function, which translates into brain fog.
Guanfacine, one of two drugs being tested in this trial, is designed to strengthen connections in the prefrontal cortex and protect against inflammation and stress, and although it was initially developed to treat ADHD, it is also used to treat other conditions related to dysfunction of the prefrontal cortex, and studies indicate that the drug is effective in restoring executive functioning and memory. NAC, the other drug, acts as a powerful antioxidant and anti-inflammatory that can also be used to treat this neural area.
Fesharaki-Zadeh has been treating his traumatic brain injury and PTSD patients successfully with a combination of guanfacine and NAC for years, and when he encountered his first long-term COVID patient in June 2020, he decided to use this therapeutic combination to treat post-COVID brain fog. She started with NAC and after seeing some benefits in energy and memory, she added guanfacine and saw further improvements.
Since then, this specialist has already treated 12 patients who suffered mental confusion after overcoming COVID with these drugs. Specifically, he instructed them to take 1 mg of guanfacine at bedtime and, if well tolerated, increase the dose to 2 mg after one month. In addition, the patients also took 600 mg of NAC once daily. Eight patients reported significant benefits, including improved memory, organizational skills, and the ability to multitask. In some the brain fog disappeared completely and they were able to resume their normal activities. Two others could not be followed up, and the other two discontinued treatment because of side effects such as low blood pressure and dry mouth. Investigators have subsequently changed the regimen from an immediate-release form of guanfacine to a sustained-release form, which decreases the risk of side effects.
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