Post-COVID Brain Fog Tied to Cognitive and Immunologic Risk Factors

Post-COVID Brain Fog Tied to Cognitive and Immunologic Risk Factors

Cognitive post-acute sequelae of SARS-CoV-2 (PASC), also known as “COVID brain fog,” may be affected by immunologic mechanisms and cognitive risk factors, according to a study published in the Annals of Clinical and Translational Neurology.

In a non-hospitalized setting following COVID-19 infection, some patients tend to experience cognitive symptoms while others do not, especially after a mild infection. Currently, there are no official guidelines of how to identify patients who present cognitive changes post-COVID infection. The objective of the current study was to identify clinical characteristics associated with cognitive PASC after mild COVID-19 to help explain why certain groups are at greater risk, and to also understand cognitive PASC pathogenesis.

The small study included 22 participants diagnosed with cognitive PASC who did not require hospitalization and were participants in the Long-Term Impact of Infection with Novel Coronavirus (LIINC) study, as well as 10 cognitive control individuals with no cognitive symptoms. The median age of the study’s participants was 41 years (range 19-69 years), with a median of 16 years of education, and assessment occurred a median of 10.1 months (range 2.3-19.0 months) after first COVID-19 symptom.

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Neuropsychological testing, structured neurocognitive interviews, and optional lumbar puncture (LP; 53%) to collect cerebrospinal fluid (CSF) were performed. Fisher’s exact tests were used to compare group proportions, while Mann-Whitney U-tests were used to compare continuous data.

No group differences were observed in terms of gender, age, duration of education, or race/ethnicity distribution (P >.05 for all). Those with cognitive PASC received evaluation closer to first COVID-19 symptoms (9.3 months) compared with cognitive control individuals (15.2 months; P =.01), though this did not differ for those who opted for LP. Younger age was associated with delayed cognitive PASC onset, which occurred in 43% (n=9) of the study’s participants with cognitive PASC. Those with cognitive PASC had higher numbers of preexisting cognitive risk factors than control individuals (2.5 vs 0, respectively; P =.03), as well as a greater proportion of abnormal CSF findings (77% vs 0%, respectively; P =.01).

Study limitations included a small sample size, a potential lack of generalizability among others with PASC, and a potential effect of intergroup age difference on the presence of preexisting cognitive risk factors.

The study researchers concluded that “individuals who were not hospitalized for SARS-CoV-2 infection can have variable onset of cognitive PASC symptoms associated with a greater number of preexisting cognitive risk factors and abnormal CSF findings.”

​​Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Apple AC, Oddi A, Peluso MJ, et al. Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19. Published online January 19, 2022. Ann Clin Transl Neurol. doi: 10.1002/acn3.51498

This article originally appeared on Neurology Advisor

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