Understanding the olfactory role in post-COVID cognitive and neuropsychiatric manifestations

Abstract

Introduction: Olfactory dysfunction (OD) is frequent after SARS-CoV-2 infection. The aim of this study was to examine if long-term OD is common in post-COVID condition, and the relationship between olfaction, cognition, neuropsychiatric symptoms, and disease duration in these patients.

Methods: This study included 121 participants with post-COVID condition and 51 healthy controls (HC). A comprehensive neuropsychological and neuropsychiatric assessment was conducted, encompassing various domains, including general cognition, processing speed, verbal fluency, attention, verbal memory, visual memory, visuoconstructive ability, visuospatial ability, abstraction, executive functions, anxious-depressive symptoms, general health perception, fatigue level, sleep quality, and olfaction. Statistical analyses were carried out to understand the relationship of OD with cognition, and its role as moderator variable.

Results: In total, 25% of the post-covid patients had a reduced smell capacity, while only 9.3% of HC presented OD. Post-COVID patients had statistically significantly worse cognitive performance and clinical status than HC. Verbal fluency (AUC = 0.85, p < 0.001), and attention (AUC = 0.82, p < 0.001) were the variables that best discriminate between groups. OD seemed to be a moderator between fatigue and cognition, and between disease duration and attention (β = -0.04; p = 0.014).

Discussion: The study highlights marked cognitive and neuropsychiatric sequelae in individuals post-COVID relative to HC. Olfactory impairment exhibits correlations with both cognitive performance and general health. Olfaction emerges as a potential prognostic marker owing to its moderating influence on disease severity indicators.

Keywords: cognition; neuropsychiatry; neuropsychology; olfaction; post-covid condition.

Figure 1

Cognitive performance and neuropsychiatric status in post-COVID condition and HC. (A) Cognitive performance. (B) Neuropsychiatric status. Values are shown in z-scores. A higher z indicates a better cognition or neuropsychiatric status. *p ≤ 0.05; **p ≤ 0.01; ***p ≤ 0.001. C-SSRS, Columbia Suicide Severity Rating Scale; GDS, Geriatric Depression Scale; HC, healthy controls; MFIS, Modified Fatigue Impact Scale; PSQI, Pittsburgh Sleep Quality Index; SF-36: The 36-Item Short Form Health Survey; STAI, State–Trait Anxiety Inventory.

Figure 2

ROC curve. AUC, Area Under the Curve. —Abstraction (AUC = 0.68, p < 0.001); —Attention (AUC = 0.80, p < 0.001); —Executive functions (AUC = 0.76, p < 0.001); —General cognition (AUC = 0.81 p < 0.001); —Olfactory sense (AUC = 0.63, p = 0.011); —Processing speed (AUC = 0.81, p < 0.001); —Verbal fluency (AUC = 0.85, p < 0.001); —Verbal memory (AUC = 0.76, p < 0.001); —Visual memory (AUC = 0.65, p = 0.005); —Visuoconstructive ability (AUC = 0.67, p = 0.001); —Visuospatial perception (AUC = 0.53, p = 609).

Figure 3

Olfactory assessment. (A) Raw BSIT score. (B) BSIT results by categories. *p ≤ 0.05. BSIT, Brief Smell Identification Test; HC, healthy controls.

Figure 4

Linear regression of cognitive domain. (A) Post-covid patients. (B) Post-covid women. (C) Post-covid men. BSIT: Brief Smell Identification Test; MFIS: Modified Fatigue Impact Scale; PSQI: Pittsburgh Sleep Quality Index; STAI: State–Trait Anxiety Inventory.

Figure 5

Olfaction as a moderating variable in cognitive performance. (A) Attention and disease duration. (B) Attention and general health. (C) Attention and fatigue. (D) Verbal memory and fatigue. (E) Visual memory and fatigue. All graphs are shown in z values. *p ≤ 0.05; **p ≤ 0.001; MFIS: Modified Fatigue Impact Scale; SF-36: The 36-Item Short Form Health Survey; STAI: State–Trait Anxiety Inventory.