Research ArticleCORONAVIRUS

COVID-19–related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters

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Science Translational Medicine  02 Jun 2021:
Vol. 13, Issue 596, eabf8396
DOI: 10.1126/scitranslmed.abf8396

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Sticking the nose into COVID-19

Patients with COVID-19 can develop loss of smell and/or taste. Unfortunately, the pathophysiology of these alterations remains unclear. Here, de Melo et al. examined the olfactory mucosa in patients with COVID-19 reporting loss of smell and detected SARS-CoV-2 viral particles and inflammation in multiple cell types in the olfactory neuroepithelium, including olfactory sensory neurons. Hamster infected with SARS-CoV-2 developed loss of smell that was associated with dissemination of the virus in the olfactory mucosa and CNS and with neuroinflammation. In four patients who developed persistent loss of smell, the authors detected lasting SARS-CoV-2 presence in the olfactory mucosa, suggesting that the prolonged relapsing anosmia in patients with COVID-19 could be due to persistent viral infection.


Whereas recent investigations have revealed viral, inflammatory, and vascular factors involved in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung pathogenesis, the pathophysiology of neurological disorders in coronavirus disease 2019 (COVID-19) remains poorly understood. Olfactory and taste dysfunction are common in COVID-19, especially in mildly symptomatic patients. Here, we conducted a virologic, molecular, and cellular study of the olfactory neuroepithelium of seven patients with COVID-19 presenting with acute loss of smell. We report evidence that the olfactory neuroepithelium is a major site of SARS-CoV2 infection with multiple cell types, including olfactory sensory neurons, support cells, and immune cells, becoming infected. SARS-CoV-2 replication in the olfactory neuroepithelium was associated with local inflammation. Furthermore, we showed that SARS-CoV-2 induced acute anosmia and ageusia in golden Syrian hamsters, lasting as long as the virus remained in the olfactory epithelium and the olfactory bulb. Last, olfactory mucosa sampling from patients showing long-term persistence of COVID-19–associated anosmia revealed the presence of virus transcripts and of SARS-CoV-2–infected cells, together with protracted inflammation. SARS-CoV-2 persistence and associated inflammation in the olfactory neuroepithelium may account for prolonged or relapsing symptoms of COVID-19, such as loss of smell, which should be considered for optimal medical management of this disease.

This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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