Eight patients with long COVID had their 'brain fog' lifted after taking a combination of medicines concocted by researchers at Yale University.

The combo includes guanfacine and an antioxidant called N-acetylcysteine (NAC).

Both medicines are already FDA-approved and widely available for the safe treatment of ADHD, traumatic brain injury (TBI), Tourette's syndrome, and PTSD. Neither has severe side effects, and they are well-tolerated by almost everyone.

At the moment, guanfacine and NAC have only been tested on a small cohort of long haulers, most of whom were women, but the initial signs are extremely promising. More extensive clinical trials with placebo controls are needed to confirm the drug combo actually improves brain fog.

However, given the severity and widespread nature of long COVID, the researchers think clinicians should consider prescribing guanfacine to patients. In the United States, NAC is available over the counter.

"If patients have a physician who can read our paper, we're hoping that they can access help right now," says neuroscientist Amy Arnsten.

She and her colleagues argue the combination of drugs could prove "immediately useful" to millions of desperate patients.

Currently, clinicians already commonly prescribe guanfacine for 'off-label' reasons, usually for other disorders of the prefrontal cortex. The non-stimulant drug is thought to increase activity in parts of the brain concerned with higher-order processing, improving attention, and reducing hyperactivity.

Brain fog is one of the most common symptoms of long COVID and similar illnesses like Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis (CFS/ME).

Long COVID casts a long shadow that goes far beyond a sense of mental fatigue. The lingering cognitive effects often lead to slowed thinking, memory loss, poor concentration, or feelings of confusion that can ultimately prove debilitating.

Today, many with long COVID or CFS/ME have spoken out about how their illness has made it extremely difficult – or even impossible – to live an everyday healthy life, maintain interpersonal relationships, or keep working. Brain fog is one of the most debilitating parts.

Since 2020, millions in the US have left the workforce because of their long COVID symptoms. And there's currently little doctors can do to help these patients reclaim their lives.

"There's a paucity of treatment out there for long COVID brain fog, so when I kept seeing the benefits of this treatment in patients, I felt a sense of urgency to disseminate this information," says neurologist Arman Fesharaki-Zadeh.

"You don't need to wait to be part of a research trial. You can ask your physician – these drugs are affordable and widely available."

Fesharaki-Zadeh first decided to try the drug combination after considering the inflammatory effects of SARS-CoV-2 on the human body.

His first long COVID patient came to him in June 2020 complaining of severe brain fog, and yet then, as now, there was no approved treatment for the common symptom.

So Fesharaki-Zadeh thought outside the box: What he saw in his long COVID patient was oddly similar to what he saw in patients following a concussion.

In many ways, long COVID presents like a hard knock to the head. Except, in this case, the SARS-CoV-2 virus was causing harm from within.

NAC is an anti-inflammatory agent often prescribed for TBI patients, so Fesharaki-Zadeh decided to prescribe that drug first.

The patient soon started reporting improved energy and memory.

Fesharaki-Zadeh added guanfacine to the mix, a drug that combats inflammation in the brain and seems to work in synergy with NAC.

The brain fog kept dissipating.

Researchers at Yale have since tested this drug combo on a dozen other patients with long COVID. Participants took 600 milligrams of NAC daily and 1 milligram of guanfacine at bedtime. After a month, the guanfacine dosage was increased to 2 milligrams.

All eight participants who finished the trial reported substantial benefits to their memory, organizational skills, and multi-tasking abilities. Some people lost their brain fog completely; others said they had recovered their sense of self.

Two patients had to leave the trial because they experienced low blood pressure and/or dizziness.

While no patient received a placebo, researchers say one case study proved "particularly illuminating".

A nurse with long COVID, who had to take time off work, reported significant benefits to her working memory, executive functioning, and cognitive processing speed after taking NAC and guanfacine each day. Unfortunately, the medication triggered an episode of low blood pressure, so it had to be stopped momentarily.

The nurse's concentration and brain power worsened almost immediately after the drugs were halted.

When the patient decided to go back on the drug regime again, her brain fog lifted. For a year now, researchers say she has tolerated the medication without any episodes of low blood pressure.

"This was not a placebo-controlled trial, but anecdotes like this make one more confident that the relief is really due to the drug and not the placebo effect," says Arnsten.

The team at Yale hopes their case study will lead to further clinical research.

The study was published in Neuroimmunology Reports.