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Background <p>Although the neurological sequelae of severe COVID-19 are increasingly recognized, the long-term neural impact of uncomplicated mild SARS-CoV-2 infection remains insufficiently characterized. This study investigated post-infection alterations in piriform cortex activity, a region central to olfactory processing and integrative cognitive-emotional networks, and their associations with cognitive outcomes in adults.</p> Methods <p>Fifty adults with pre- and post-SARS-CoV-2 magnetic resonance imaging (MRI) and clinical/neuropsychological data were analyzed. A demographically matched control group of 50 individuals without prior COVID-19 or vaccination was included. Resting-state functional MRI assessed amplitude of low-frequency fluctuations (ALFF) within the piriform cortex as an index of regional neural activity.</p> Results <p>Baseline piriform ALFF did not differ between the two groups (<i>p</i> = 0.421). Following infection, piriform ALFF exhibited a significant quadratic trajectory (<i>p</i> = 0.003), characterized by early elevation relative to baseline, a decline to a nadir at approximately three months, and subsequent recovery toward baseline levels by six months. Greater acute COVID-19 symptom burden correlated with higher piriform ALFF (<i>β</i> = 0.34, <i>p</i> = 0.017). Elevated ALFF was associated with reduced processing speed (<i>β </i>= -0.52, <i>p</i> = 0.001). Mediation analysis demonstrated that piriform ALFF significantly mediated the relationship between symptom burden and processing speed (indirect effect <i>b </i>= -0.081, <i>p</i> = 0.037).</p> Conclusions <p>Piriform cortex function demonstrated a dynamic, nonlinear pattern within six months after mild COVID-19, marked by early hyperactivity, later downregulation, and gradual normalization. Altered piriform activity mediated the association between symptom burden and processing speed deficits, suggesting transient post-infection neurophysiological disruption with potential relevance to cognitive symptoms. Longitudinal follow-up is warranted to clarify underlying mechanisms and long-term implications.</p>

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Dynamic recovery of piriform cortex function and its impact on cognitive processing speed following mild COVID-19

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月6日

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  • Hyeonseok Jeong,
  • Youngeun Shim,
  • Yoonji Joo,
  • Yejin Kim,
  • Chaewon Suh,
  • Yunjung Jin,
  • Harin Song,
  • In Kyoon Lyoo,
  • Sujung Yoon

摘要

Background

Although the neurological sequelae of severe COVID-19 are increasingly recognized, the long-term neural impact of uncomplicated mild SARS-CoV-2 infection remains insufficiently characterized. This study investigated post-infection alterations in piriform cortex activity, a region central to olfactory processing and integrative cognitive-emotional networks, and their associations with cognitive outcomes in adults.

Methods

Fifty adults with pre- and post-SARS-CoV-2 magnetic resonance imaging (MRI) and clinical/neuropsychological data were analyzed. A demographically matched control group of 50 individuals without prior COVID-19 or vaccination was included. Resting-state functional MRI assessed amplitude of low-frequency fluctuations (ALFF) within the piriform cortex as an index of regional neural activity.

Results

Baseline piriform ALFF did not differ between the two groups (p = 0.421). Following infection, piriform ALFF exhibited a significant quadratic trajectory (p = 0.003), characterized by early elevation relative to baseline, a decline to a nadir at approximately three months, and subsequent recovery toward baseline levels by six months. Greater acute COVID-19 symptom burden correlated with higher piriform ALFF (β = 0.34, p = 0.017). Elevated ALFF was associated with reduced processing speed (β = -0.52, p = 0.001). Mediation analysis demonstrated that piriform ALFF significantly mediated the relationship between symptom burden and processing speed (indirect effect b = -0.081, p = 0.037).

Conclusions

Piriform cortex function demonstrated a dynamic, nonlinear pattern within six months after mild COVID-19, marked by early hyperactivity, later downregulation, and gradual normalization. Altered piriform activity mediated the association between symptom burden and processing speed deficits, suggesting transient post-infection neurophysiological disruption with potential relevance to cognitive symptoms. Longitudinal follow-up is warranted to clarify underlying mechanisms and long-term implications.