November 20, 2023
Dr. Henry Mahncke

CEO of Posit Science, developers of the BrainHQ brain training program. Focused on digital health and bringing science to the people.

From the earliest days of the Covid-19 pandemic, it’s been clear that recovery from Covid was different from recovery in many other illnesses. Lots of people who had come down with the virus recovered from the initial symptoms like coughing and shortness of breath—but didn’t get fully better.

As a neuroscientist and as a researcher focused on brain health, I watched these initial reports with interest and concern. Many of the symptoms reported were brain health symptoms—problems with concentration, working memory and a general feeling of “brain fog.”

This constellation of symptoms was worryingly familiar. I am the CEO of Posit Science, where we make a brain training program called BrainHQ. BrainHQ has dozens of brain training exercises built on the principles of brain plasticity to rewire the brain—helping people think faster, focus better and remember more—while improving brain health and building brain resilience. We and our scientific collaborators have published more than 200 papers showing that this approach works.

Over time, more and more academic researchers have used BrainHQ with all kinds of brain health conditions. And what I learned from those researchers is that a lot of medical conditions, like multiple sclerosis, cancer treatment, concussion and heart failure, all can lead to “brain fog.”

The story behind the scientific understanding in each medical condition was similar. First, there were patient reports of “brain fog.” Initially, these reports weren’t taken very seriously by doctors. After all, such patients had serious health conditions, and “brain fog” didn’t seem very significant by comparison. It was easy to say that many of these symptoms were “all in your head.”

But cognitive impairment doesn’t work that way. You can’t just tell a person with brain fog to just start thinking more clearly any more than you can tell a person with a fractured leg to just walk harder.

Thankfully, as these conditions have been studied more by researchers they have been taken more seriously by clinicians.

Long Covid—the constellation of health symptoms experienced by many people—has followed an accelerated version of this pathway, and that represents some real progress. The first patient reports of long Covid were as early as May 2020—just a few months after the worldwide pandemic shutdown began. Those reports, including complaints of brain fog, were generally taken seriously by the medical community and the popular press.

I was heartened when the NIH announced the RECOVER initiative—a multibillion-dollar effort to study the symptoms of long Covid, recruiting patients across the country, and deploying an arsenal of tests to figure out which symptoms were most common, which symptoms clustered together, and which symptoms caused the most real-world problems for patients.

Evaluating these symptoms in observational studies is a good first step, but it’s not enough. People with long Covid deserve safe, effective treatments for their complex symptoms. And to develop those treatments, we need randomized controlled trials to see what works and who it works for (and also, importantly, what doesn’t work).

And just recently, the RECOVER initiative announced the next big step: the first clinical trials of interventions that might help people with long Covid. Four trials have been announced—RECOVER-VITAL (removing persistent viral infections), RECOVER-SLEEP (excessive daytime sleepiness and difficulties falling asleep), RECOVER-AUTONOMIC (issues arising from the autonomic nervous system, which controls basic functions throughout the body) and RECOVER-NEURO (brain fog).

I’m honored to say that the RECOVER-NEURO trial selected BrainHQ as one of the interventions to be tested in the RECOVER-NEURO trial, along with a web-based goal management training program (developed at Mount Sinai Health System) and a transcranial direct current stimulation system (developed by Soterix Medical).

The RECOVER-NEURO trial is an important next step. But it’s also not enough.

That’s because no treatment for the cognitive symptoms of long Covid can be made generally available to patients until the FDA approves the treatment. And remarkably, despite billions already spent on long Covid research, there isn’t yet a consensus among patients, clinicians and the FDA on two key issues:

  • How should a patient be diagnosed with cognitive symptoms after Covid? Is it enough if the patient says that they have brain fog? Or should they have to take a cognitive test, and show a specific level of impairment? What about people with high cognitive performance before Covid, who have declined to “average” levels?
  • How should clinicians evaluate the effects of treatments? Are there specific cognitive tests that are most sensitive? How big a change on these tests is “big enough” to show benefit?

The FDA has held initial meetings on this topic—but we don’t yet have clear answers. That means those developing innovative treatments and health technology solutions for cognitive symptoms in long Covid—be they new drugs, or old drugs with a new purpose, or medical devices, or brain training programs (as I do) can’t make much progress until these standards get worked out and defined.

So what can you do if you are involved as a leader at a health care insurer, a health care provider group or a health tech organization and you want to see faster progress on these issues?

First, listen to your patients. Their concerns about the long-term effects of Covid are real, and they deserve your help. Second, consider establishing a long Covid clinic, like UCSF, Stanford and Mount Sinai already have, because these patients have complex care needs, best handled by a multidisciplinary clinical team that is empowered to evaluate innovative practices that can offer hope—and help—to patients. Third, let key government officials hear from you—and let them know that we need clarity on the path forward from federal regulatory agencies.

And finally, keep fighting. If the earliest patients with long Covid symptoms had given up, we would be where we are today with results from the RECOVER studies coming out and the first trials starting.