New Study Finds Post-COVID Brain Fog Is Real: HV Patch Q&A

HUDSON VALLEY, NY — A new study suggests links between COVID-19 and the problems commonly referred to as “brain fog," according to researchers at New York Medical College.

Patients reporting these symptoms — diminished focus and mental clarity, forgetfulness, mental fatigue and difficulty making decisions and multitasking — after infection should be taken seriously, said Dr. Stephen Ferrando, lead author on the study recently published in the Journal of the Academy of Consultation-Liaison Psychiatry.

"Brain fog is a term that has been heard a lot recently. You have patients saying, ‘My thinking is fuzzy. I can't remember things. I have words on the tip of my tongue, but I can't think of them. I'm tired all the time,’" said Ferrando, Har Esh Professor and chair of the Department of Psychiatry and Behavioral Sciences at NYMC in Valhalla, New York.

The study led 60 participants through neuropsychological, psychiatric, medical, functional and quality-of-life assessments six to eight months after suffering from COVID-19. Those already seeking care for "brain fog" showed poor performance in key neurocognitive areas, as well as high levels of clinically significant depression and fatigue, along with overall diminished quality of life.

Prior studies using different methods found patients did not show significant deficits but were more likely to be anxious and depressed, Ferrando said.

"However, in the neuropsychological testing we conducted, we found that many of these individuals were in fact not thinking clearly and it was not just about depression or medical comorbidities but something that the virus was doing in the brain that leads to residual cognitive problems," he said. "So, the takeaway message is that for patients who are complaining of post-COVID-19 cognitive issues, there may very well be something there. These complaints are not imagined. They are not psychosomatic and they need to be taken seriously.”

In the study, participants seeking care for cognitive complaints were compared with participants who were not.

“One unique aspect of our study was that unlike other studies that were conducted online, we conducted this very detailed assessment in person,” Ferrando said. “Even during the height of the pandemic, we were seeing people face to face and testing them."

Though their first study on the topic is newly published, the team of researchers — made up of NYMC faculty, residents and students — is already conducting further research.

"I think that's the biggest next step is longitudinal,” he said. "We are now looking at whether these individuals have improved or not, and if not why? What are some predictors? In terms of their vaccination status, has that helped or hindered? We can also now look at work functioning, which is very important, because a lot of people took substantial time off work but are now back at work, and they're struggling."

Ferrando offered more insights during a Q&A with Patch:

PATCH: Diminished quality of life sounds depressing. How did researchers find the study participants characterizing that?

DR. FERRANDO: Yes, we were very interested in the individual experiences of the study participants, particularly their mood and anxiety, their ability to function and their quality of life.
We are currently analyzing our quality of life data and plan on publishing a separate report on this, however, interestingly, we found that the top 5 areas of diminished quality of life included decreased satisfaction with sexual interest, pleasure and drive; mood; work; household activities; and physical health.

A typical narrative of the study participants was that they were “not the same” in the months after COVID, that they were struggling with fatigue, difficulty with their ability to think and perform complex tasks, low mood and a sense of lack of empathy and understanding from others, including their family and physicians, who had minimized or dismissed their complaints.

PATCH: How could researchers tell it was something that the virus was doing?

DR. FERRANDO: At this point, we cannot determine causation, and there are a number of factors that need to be taken into consideration. One important clue to a viral cause is that neurocognitive deficits were correlated with severity of acute COVID illness. It has been documented by us and others that the sicker an individual was when they were first infected with coronavirus, the more likely they are to have neurocognitive deficits, even months later.

Other factors play a role, however, including depression. In the article, we discuss the close association between diminished cognitive function and depression. Again, the causal link here is not clear and is very difficult to tease out. We hypothesize that there is a shared mechanism that is related to severity of viral infection and persistent inflammation in the body (and brain) that leads to both symptoms of depression and neurocognitive dysfunction. Of course, the relationship is very complex and there are many other factors that likely played a role in both entities, including extreme psychosocial stressors caused by the pandemic and viral infection itself, as well as medical comorbidities such as obesity, diabetes and high blood pressure.

PATCH: How does one measure significant depression?

DR. FERRANDO: In this study, we used a clinical questionnaire, the Patient Health Questionnaire-9 (PHQ-9), which is used around the world to screen for both the diagnosis and severity of depression. This questionnaire is used in the primary care doctor's office, is in the public domain, and is available to the public, so that self-screening is possible. Importantly, it has cutoff scores to determine levels of clinical depression, including no depression, minimal - , mild-, moderate – and severe depression.

PATCH: What are key neurocognitive areas, and what did researchers find where?

DR. FERRANDO: This is a very important question. The neurocognitive areas that we found to be affected, particularly those in our Post-COVID Recovery Program who were complaining of “brain fog,” included difficulty (as compared to population-based normative values) with attention and concentration, slowed thinking and information processing, diminished memory (particularly delayed memory) and decreased executive function (ability to plan, organize and multi-task).

These areas of neurocognitive function are important to our everyday ability to maintain independent activities of daily living as well as our ability to study and work.

Importantly, the diminished performance we found in these neurocognitive areas correlated well with perceived difficulty in cognitive functioning as well as reported difficulties in everyday and occupational functioning.

PATCH: How did researchers' testing differ from the standard neuropsychological testing battery?

DR. FERRANDO: The neuropsychological testing battery used in this study consisted of standard neuropsychological tests covering the key neurocognitive domains (attention/concentration, speed of information processing, short- and long-term memory, language and executive function), but was briefer (approximately 40 minutes) than the typically utilized clinical neuropsychological test battery, which takes 2-6 hours to administer. The study demonstrated that this abbreviated battery was user-friendly and yielded robust information about the clinical relevance of the neuropsychological test findings. One important advantage of this study was that participants were recruited both from the community and from a specialized Post-COVID Recovery Program at WMC Health, so that we were in a position to compare individuals who were seeking care for post-COVID “brain fog” to those who were not seeking care. Further, participants were assessed in person during the pandemic, while many other neurocognitive studies in the literature included assessments that were less complete, were conducted on line or over the telephone.

Finally, one of the most important aspects of the study was that we utilized validated assessments of both subjective and objective cognitive function. We showed that people who perceive that they have cognitive problems do indeed perform more poorly on neuropsychological testing, so that their perception of difficulty should not be dismissed. Other studies, both post-COVID and in other disease entities (i.e., MS, HIV) have not consistently shown a correlation between perceived and objective performance.

PATCH: Can you say anything about what researchers are seeing in your continuing studies?

DR. FERRANDO: We are currently recruiting a new cohort of participants who were affected by the Omicron variant since late December of 2021. We are interested to see if individuals infected with this strain of the virus had similar post-COVID symptoms. We are also following up participants from this publication and are almost finished with our 6-month assessment (and then 1 year later at 18 months).

We will be analyzing and publishing these data in the coming months, but unfortunately, no results as yet.

We are also engaged in several sub-studies, including post-COVID depression, anxiety/PTSD, quality of life, and work/occupational function. We are interested in describing the characteristics and causes of diminished outcomes in all of these areas, as well as factors that protect individuals from developing these problems (activity, vaccination) or treat them once they occur (i.e., neurocognitive rehabilitation, psychotherapies, psychopharmacological treatments).