SCIENCE@home

Olfactory Dysfunction and Cognitive Deterioration in Long COVID: Pathomechanisms and Clinical Implications in Development of Alzheimer’s Disease

E. Stigliano,Aurora Tocci,Rita Florio,V. Arena,G. Amadoro

Published 2026 in Cells

ABSTRACT

Highlights What are the main findings? Neurological complications, including loss of smell, cognitive and psychiatric symptoms, contribute to long COVID syndrome. A correlation exists between persistent anosmia and clinical dementia in patients who experienced SARS-CoV-2 infection. What are the implications of the main findings? SARS-CoV-2 infection of olfactory neuroepithelium may contribute to degeneration of limbic and cortical brain areas and, then, to the onset of Alzheimer’s Disease (AD). Interventions for treatment of SARS-CoV-2-mediated chronic olfactory dysfunction are required to improve brain and mental health in COVID-19 survivors. Abstract Complete or partial loss of smell (anosmia), sometimes in association with distorted olfactory perceptions (parosmia), is a common neurological symptom affecting nearly 60% of patients suffering from post-acute neurological sequelae of COronaVIrus Disease of 2019 (COVID-19) syndrome, called long COVID. Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) may gain access from the nasal cavity to the brain (neurotropism), and the olfactory route has been proposed as a peripheral site of virus entry. COVID-19 is a risk factor for developing Alzheimer’s Disease (AD), an age-dependent and progressive neurodegenerative disorder characterized in affected patients by early olfaction dysfunction that precedes signs of cognitive decline associated with neurodegeneration in vulnerable brain regions of their limbic system. Here, we summarize the recent literature data supporting the causal correlation between the persistent olfactory deterioration following SARS-CoV-2 infection and the long-delayed manifestation of AD-like memory impairment. SARS-CoV-2 infection of the olfactory neuroepithelium is likely to trigger a pattern of detrimental events that, directly and/or indirectly, affect the anatomically interconnected hippocampal and cortical areas, thus resulting in tardive clinical dementia. We also delineate future advancement on pharmacological and rehabilitative treatments to improve the olfactory dysfunction in patients recovering even from the acute/mild phase of COVID-19. Collectively, the present review aims at highlighting the physiopathological nexus between COVID-19 anosmia and post-pandemic mental health to favor the development of best-targeted and more effective therapeutic strategies in the fight against the long-term neurological complications associated with SARS-CoV-2 infection.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-100 of 233 references · Page 1 of 3

123
Next

CITED BY