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.
Highlights
COVID-19 has affected more than 275,000,000 people worldwide, with a wide range in clinical presentation and duration of symptoms
Persistent smell alteration was present for a mean period of 9.8 + 2.8 months after a negaPersistent smell alteration was present for a mean period of 9.8 + 2.8 months after a negative tive swab for SARS-CoV-2
Smell alterations are attributed to neuroinflammation of the olfactory bulb [16] and women, perhaps more predisposed toinflammation, already have a higher baseline rate of olfactory bulbs atrophy with aging compared with men in the same age range [17]
Summary
COVID-19 has affected more than 275,000,000 people worldwide, with a wide range in clinical presentation and duration of symptoms. Considered primarily a respiratory illness, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is recognized as a multi-organ disease. The infection, spreading from the nasopharynx into the brain [1,2], causes anosmia [3] and several neurologic symptoms [4,5], ranging from impaired executive function to hearing and vestibular dysfunction [1]. Persistence of neurologic symptoms is more common than initially recognized [1,4,5]. The propensity of SARS-CoV-2 to cause post-acute symptoms, such as fatigue, headache, altered memory/thinking, and joint pain or muscle aches, has led to coining of the term “Long-COVID Syndrome”, when symptoms persist over 6 months after swab negativization [6]. Referred to as long-haul COVID, or post-acute COVID-19 [7], the entity remains poorly understood and much work remains in refining the diagnosis, etiology, associations, and management of this evolving concept, despite several authors’
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