COVID-19 anosmia pathogenesis based on 18F-FDG PET studies

Introduction: Hyposmia (diminished sense of smell) and anosmia (total loss of the sense of smell) have been reported as relatively common complications in patients with coronavirus disease-2019 (COVID-19) infection. Unlike the loss of smell or taste in common viral rhinitis, the hyposmia/anosmia of COVID-19 is reported to happen in the absence of nasal congestion or paranasal sinuses abnormality. Moreover, anosmia in COVID-19 may last for weeks to months following the COVID-19 acute phase. In this study, we tried to investigate the potential pathogenesis of hyposmia or anosmia in COVID-19 infection based on ¹⁸F-FDG PET brain studies.

Methods: A comprehensive literature review was performed in the MEDLINE, Embase, Cochrane library databases, and Web of Science. The search results were screened for English studies including case reports/series, cohort studies, and clinical trials regarding brain imaging in patients with COVID-19 infection and anosmia, hyposmia, or parosmia without any publication date limitation. Included papers were reviewed regarding the study design, patient population, and outcomes.

Results: Magnetic resonance imaging (MRI) of patients with COVID-19 induced anosmia were mostly reported normal in both morphology and signal intensity of the olfactory bulb. Moreover, paranasal sinuses were reported normal in CT scan studies. However, ¹⁸F-FDG PET studies showed a reduction of glucose uptake in the dominant orbitofrontal cortex, insula, inferior frontal gyrus, and cerebellar vermis. Same pathological patterns were also reported in the ¹⁸F-FDG PET studies of cases with parosmia (dysfunctional smell detection) following COVID-19 infection.

The pathological patterns reported in brain ¹⁸F-FDG-PET studies can be explained by the impaired neural function due to direct neurotropism of severe acute respiratory syndrome coronavirus 2 (sars-CoV-2) due to expression of angiotensin-converting enzyme 2 (ACE2) on the nervous system cells, especially in the olfactory cortex.

Conclusions: Anosmia has been reported as one of the complications following the acute course of COVID-19 infection. ¹⁸F-FDG PET studies of patients with COVID-19 induced hyposmia, anosmia or parosmia showed decreased metabolic activity of the orbitofrontal cortex which can be a result of direct viral neurotropism. More ¹⁸F-FDG PET studies can help us in a better understanding of the reletivley long lasting neurologic complications of COVID-19.