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. 2022 Jan 24;12(2):154.
doi: 10.3390/brainsci12020154.

Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study

Arianna Di Stadio  1 , Michael J Brenner  2 , Pietro De Luca  3 , Maria Albanese  4 , Luca D'Ascanio  5 , Massimo Ralli  6 , Dalila Roccamatisi  7 , Cristina Cingolani  5 , Federica Vitelli  5 , Angelo Camaioni  8 , Stefano Di Girolamo  9 , Evanthia Bernitsas  10
Affiliations

Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study

Arianna Di Stadio et al. Brain Sci. .

Abstract

Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms.

Keywords: COVID-19; SARS-CoV-2; brain fog; cognitive deficit; headache; mental clouding; neuroinflammation; olfaction; olfactory dysfunction; smell.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
(A) Distribution for age of different Sniffin’ scores in women. (B) Distribution for age of different Sniffin’ scores in men. The boxes in red, yellow, and green color represent the normal range for general population in term of normality, hypofunction or absence of smell capacity. Dots in the red boxes are indicative of anosmia, in the yellow are of hyposmia, and in the green are of normosmia. The reference value for normal olfactory scores refers to the data published by Oleszkiewicz et al. [14].
Figure 2
Figure 2
Distribution of neurological symptoms and smell alterations.
Figure 3
Figure 3
Distribution of mental clouding (brain fog) (presence and absence) relative to the different smell alterations.
Figure 4
Figure 4
Shows smell alterations patients that reported headache.
Figure 5
Figure 5
Smell alterations patients who reported both mental clouding and headache.
See this image and copyright information in PMC

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