Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

Jed Wingrove; Janine Makaronidis; Ferran Prados; Baris Kanber; Marios C Yiannakas; Cormac Magee; Gloria Castellazzi; Louis Grandjean; Xavier Golay; Carmen Tur; Olga Ciccarelli; Egidio D'Angelo; Claudia A M Gandini Wheeler-Kingshott; Rachel L Batterham

doi:10.1016/j.eclinm.2023.101883

Aberrant olfactory network functional connectivity in people with olfactory dysfunction following COVID-19 infection: an exploratory, observational study

EClinicalMedicine. 2023 Apr:58:101883. doi: 10.1016/j.eclinm.2023.101883. Epub 2023 Mar 2.

Authors

Jed Wingrove^{1

2}, Janine Makaronidis^{1

2}, Ferran Prados^{2

3

4}, Baris Kanber^{2

3

4}, Marios C Yiannakas³, Cormac Magee^{1

2}, Gloria Castellazzi^{3

5}, Louis Grandjean⁶, Xavier Golay^{3

7}, Carmen Tur³, Olga Ciccarelli^{2

3}, Egidio D'Angelo^{5

8}, Claudia A M Gandini Wheeler-Kingshott^{3

5

8}, Rachel L Batterham^{1

2}

Affiliations

¹ Centre for Obesity Research, Department of Medicine, University College London, London, UK.
² National Institute for Health and Care Research, Biomedical Research Centre at UCLH and UCL, London, UK.
³ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁴ Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
⁵ Brain Connectivity Research Centre, IRCCS Mondino Foundation, Pavia, Italy.
⁶ Department of Infection, Immunity & Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
⁷ Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, UK.
⁸ Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.

Abstract

Background: Olfactory impairments and anosmia from COVID-19 infection typically resolve within 2-4 weeks, although in some cases, symptoms persist longer. COVID-19-related anosmia is associated with olfactory bulb atrophy, however, the impact on cortical structures is relatively unknown, particularly in those with long-term symptoms.

Methods: In this exploratory, observational study, we studied individuals who experienced COVID-19-related anosmia, with or without recovered sense of smell, and compared against individuals with no prior COVID-19 infection (confirmed by antibody testing, all vaccine naïve). MRI Imaging was carried out between the 15th July and 17th November 2020 at the Queen Square House Clinical Scanning Facility, UCL, United Kingdom. Using functional magnetic resonance imaging (fMRI) and structural imaging, we assessed differences in functional connectivity (FC) between olfactory regions, whole brain grey matter (GM) cerebral blood flow (CBF) and GM density.

Findings: Individuals with anosmia showed increased FC between the left orbitofrontal cortex (OFC), visual association cortex and cerebellum and FC reductions between the right OFC and dorsal anterior cingulate cortex compared to those with no prior COVID-19 infection (p < 0.05, from whole brain statistical parametric map analysis). Individuals with anosmia also showed greater CBF in the left insula, hippocampus and ventral posterior cingulate when compared to those with resolved anosmia (p < 0.05, from whole brain statistical parametric map analysis).

Interpretation: This work describes, for the first time to our knowledge, functional differences within olfactory areas and regions involved in sensory processing and cognitive functioning. This work identifies key areas for further research and potential target sites for therapeutic strategies.

Funding: This study was funded by the National Institute for Health and Care Research and supported by the Queen Square Scanner business case.

Keywords: COVID-19 anosmia; Cerebral blood flow; Functional neuroimaging; Olfactory impairments; Olfactory networks; Resting state connectivity.