Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study, 2022, Chen et al

Highlights

• Neuropsychiatric symptoms are often reported following COVID-19 infection.
• Self-reported symptoms may not be associated with objective dysfunction.
• Self-reported symptoms may be associated with depression and anxiety.
• Cognitive testing may overestimate clinical impairment in disadvantaged populations.

Abstract

Background
As the coronavirus disease 2019 (COVID-19) pandemic continues, there has been a growing interest in the chronic sequelae of COVID-19. Neuropsychiatric symptoms are observed in the acute phase of infection, but there is a need for accurate characterization of how these symptoms evolve over time. Additionally, African American populations have been disproportionately affected by the COVID-19 pandemic. The COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia (CONGA) was established to investigate the severity and chronicity of these neurologic findings over the five-year period following infection.

Methods
The CONGA study aims to recruit COVID-19 positive adult patients in Georgia, United States from both the inpatient and outpatient setting, with 50% being African American. This paper reports our preliminary results from the baseline visits of the first 200 patients recruited who were on average 125 days since having a positive COVID-19 test. The demographics, self-reported symptoms, comorbidities, and quantitative measures of depression, anxiety, smell, taste, and cognition were analyzed. Cognitive measures were compared to demographically matched controls. Blood and mononuclear cells were drawn and stored for future analysis.

Results
Fatigue was the most reported symptom in the study cohort (68.5%). Thirty percent of participants demonstrated hyposmia and 30% of participants demonstrated hypogeusia. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety. The study cohort performed worse on cognitive measures compared to demographically matched controls, and African American patients scored lower compared to non-Hispanic White patients on all quantitative cognitive testing.

Conclusion
Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infection. Our results suggest that self-reported neurologic symptoms do not appear to correlate with associated quantitative dysfunction, emphasizing the importance of quantitative measurements in the complete assessment of deficits. Self-reported symptoms are associated with depression and anxiety. COVID-19 infection appears to be associated with worse performance on cognitive measures, though the disparity in score between African American patients and non-Hispanic White patients is likely largely due to psychosocial, physical health, and socioeconomic factors.

Open access, https://www.sciencedirect.com/science/article/pii/S2666354622000813

 

Patients underwent the following cognitive tests:

- Montreal Cognitive Assessment, which can be completed in approx. 10 minutes (https://geriatrictoolkit.missouri.edu/cog/MoCA-8.3-English-Test-2018-04.pdf)

- Working memory & language tests from the NIH Toolbox, which can be completed respectively in approx. 7 and 4 minutes (https://www.healthmeasures.net/expl...ms/nih-toolbox/intro-to-nih-toolbox/cognition)

These short tests can’t assess cognitive performance on a complex task such as reasoning for 20 or 30 minutes on a problem at work, which may have been what participants experience in their daily life. I suspect that the participants who reported cognitive symptoms would have fared worse on a longer battery of cognitive tests. It would have been useful to have a qualitative assessment of the participants’ cognitive symptoms.

Personally, when I underwent a battery of cognitive tests during a neuropsychological evaluation that lasted almost 2 hours, I performed decently well at the beginning but could do less and less as time went on. Eventually, I was confusing colour names, could not recall a picture or memorize simple words, etc. I left the neuropsychologist’s office with a bad headache and had difficulty listening to people and constructing sentences afterwards.

Despite this limitation (which is not acknowledged by the authors), they propose that long Covid brain fog is psychiatric in nature:

“Given the high prevalence of depression after COVID-19 infection related to both the psychosocial effects of the COVID-19 pandemic as well as the implications of the virus’ long-term effects, it is possible that a proportion of patients endorsing subjective cognitive impairment may have other underlying psychiatric factors which may be contributing towards brain fog symptoms.”

As for olfaction, the authors note that their tests were limited in their ability to detect changes other than loss of smell:

“Additionally, the higher prevalence of self-reported olfactory and gustatory deficits compared to quantitative testing highlights how the change in smell and taste associated with COVID-19 may manifest as qualitative changes. Such changes may include parosmias such as dysosmias and phantosmias rather than simply the absence of these senses, which may not be as readily apparent with our quantitative tests (Hummel et al., 2011). This may explain why those who still self-reported persistent smell and taste abnormalities still scored within the normal range on the UPSIT and WETT.”

 

As the saying goes, if you cannot measure what is important , make important what you can measure.