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

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.

Correlations between Persistent Olfactory and Semantic Memory Disorders after SARS-CoV-2 Infection

“…This is in line with results found in previous studies, revealing the association of olfactory and cognitive abilities in post COVID-19 patients [ 29 , 71 , 72 ]. In addition, it was also suggested that the more COVID-19 symptoms were more severe and persistent, such as olfactory impairment, the more cognitive impairment was higher [ 29 , 62 , 72 ]. Our results support this observation: the higher were TODA threshold scores, revealing deteriorated olfactory perception, the lower were PPTT scores.…”

“…Several studies have also shown an impairment of executive functions [ 20 , 25 , 28 , 29 , 30 , 31 , 32 , 33 ] attention [ 20 , 26 , 28 , 30 , 32 , 33 ] and memory [ 24 , 27 , 30 , 32 , 33 ] following COVID-19. In our study, we found that for the 40–59 age group, generative naming time was correlated with PPTT scores: the longer the generative naming time, the better the PPTT scores.…”

“…A recent study using pre- and post-infection imaging data identified a reduction in grey matter thickness, especially in the left hemisphere, and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, which are highly connected to the olfactory system [ 26 ]. The damage to certain brain regions as a result of SARS-CoV-2 infection seems to lead to cognitive dysfunction [ 20 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. Indeed, the percentage of post COVID-19 patients with global cognitive impairment varies from 15 to 80% [ 31 ].…”

“…Indeed, the percentage of post COVID-19 patients with global cognitive impairment varies from 15 to 80% [ 31 ]. This cognitive dysfunction results in executive disorders [ 20 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ], attentional disorders [ 20 , 26 , 28 , 30 , 32 , 33 ], memory disorders [ 24 , 27 , 28 , 30 , 32 , 33 ], and sometimes language disorders regarding semantic and phonological verbal fluency [ 25 , 30 , 32 , 33 ].…”

Headache and infections of the central nervous system: neuroradiology

“…Headache, anosmia, and ageusia are frequent neurological symptoms. [9][10][11][12][13][14][15][16][17][18][19][20] Patients with Corona-19 virus disease (Covid-19) may present neurological symptoms with repercussions on imaging exams; and an association with ischemic infarction has been described 21,22 , as well as hemorrhagic lesions 23 , acute hemorrhagic necrotizing encephalopathy 24 , cerebral venous thrombosis 25 , and diffuse leukoencephalopathy with microhemorrhage. 26 Microhemorrhagic lesions and impregnation in the olfactory bulbs of patients with Covid-19 with or without anosmia have been described using the "coronal technique with thin T1 cuts with fat suppression in the anterior cranial fossa" pre-and post-contrast.…”