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Related Experiment Video

Updated: May 28, 2026

Pupillary Response as Assessment of Effective Seizure Induction by Electroconvulsive Therapy
04:51

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Published on: April 11, 2019

Task-Evoked Pupillary Dynamics Are Altered in Post-COVID Syndrome.

Alexander Smit1, Philipp Fleischmann1, Thomas S Knauer1

  • 1Department of Ophthalmology, University Hospital, Friedrich Alexander University Erlangen-Nuremberg, 91054 Erlangen, Germany.

Medical Sciences (Basel, Switzerland)
|May 27, 2026
PubMed
Summary

Post-COVID syndrome (PCS) patients exhibit lower pupillary activity indices (IPA and LHIPA) during cognitive tasks compared to controls. These findings suggest altered cognitive load processing and autonomic regulation in PCS, potentially aiding objective assessment.

Keywords:
Index of Pupillary Activity (IPA)Long COVIDLow/High Index of Pupillary Activity (LHIPA)Post-COVID syndromeautonomic nervous systemcognitive loadpupillometryvirtual reality-based assessment

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Area of Science:

  • Neuroscience
  • Ophthalmology
  • Cognitive Science

Background:

  • Persistent cognitive complaints like fatigue and impaired concentration are common in Post-COVID syndrome (PCS).
  • Objective markers for cognitive dysfunction in PCS are currently lacking.
  • Pupillary oscillation metrics (IPA, LHIPA) are emerging as non-invasive indicators of cognitive load and autonomic regulation.

Purpose of the Study:

  • To investigate the Index of Pupillary Activity (IPA) and Low/High Index of Pupillary Activity (LHIPA) in a large cohort of PCS patients versus healthy controls.
  • To assess pupillary dynamics as potential objective markers for cognitive dysfunction in Post-COVID syndrome.

Main Methods:

  • A cross-sectional study involving 397 PCS patients and 129 healthy controls.
  • Participants performed a virtual reality stereoscopic task at varying difficulty levels while eye tracking data was collected.
  • Continuous pupillometry data were analyzed to calculate IPA and LHIPA, with statistical models adjusting for age, sex, and task difficulty.

Main Results:

  • Both IPA and LHIPA were significantly lower in PCS patients compared to controls across all task difficulties.
  • Adjusted models confirmed lower overall IPA and LHIPA in PCS patients.
  • Both indices showed an inverse association with task difficulty, with higher values at lower difficulties.

Conclusions:

  • Post-COVID syndrome is associated with reduced IPA and LHIPA during cognitive tasks.
  • These findings suggest altered task-related pupillary dynamics, reflecting impaired cognitive-load processing and autonomic regulation in PCS.
  • LHIPA, and potentially IPA, may serve as objective measures for assessing task-related pupillary alterations in Post-COVID syndrome.