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. 2024 Apr 9;12(4):830.
doi: 10.3390/biomedicines12040830.

SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs

Marco Dell'Aquila  1   2 , Concetta Cafiero  3   4 , Alessandra Micera  5 , Egidio Stigliano  1 , Maria Pia Ottaiano  6 , Giulio Benincasa  6 , Beniamino Schiavone  6 , Leo Guidobaldi  7 , Luigi Santacroce  8 , Salvatore Pisconti  3 , Vincenzo Arena  1 , Raffaele Palmirotta  9
Affiliations

SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs

Marco Dell'Aquila et al. Biomedicines. .

Abstract

Background: The COVID-19 pandemic has been a health emergency with a significant impact on the world due to its high infectiousness. The disease, primarily identified in the lower respiratory tract, develops with numerous clinical symptoms affecting multiple organs and displays a clinical finding of anosmia. Several authors have investigated the pathogenetic mechanisms of the olfactory disturbances caused by SARS-CoV-2 infection, proposing different hypotheses and showing contradictory results. Since uncertainties remain about possible virus neurotropism and direct damage to the olfactory bulb, we investigated the expression of SARS-CoV-2 as well as ACE2 receptor transcripts in autoptic lung and olfactory bulb tissues, with respect to the histopathological features.

Methods: Twenty-five COVID-19 olfactory bulbs and lung tissues were randomly collected from 200 initial autopsies performed during the COVID-19 pandemic. Routine diagnosis was based on clinical and radiological findings and were confirmed with post-mortem swabs. Real-time RT-PCR for SARS-CoV-2 and ACE2 receptor RNA was carried out on autoptic FFPE lung and olfactory bulb tissues. Histological staining was performed on tissue specimens and compared with the molecular data.

Results: While real-time RT-PCR for SARS-CoV-2 was positive in 23 out of 25 lung samples, the viral RNA expression was absent in olfactory bulbs. ACE2-receptor RNA was present in all tissues examined, being highly expressed in lung samples than olfactory bulbs.

Conclusions: Our finding suggests that COVID-19 anosmia is not only due to neurotropism and the direct action of SARS-CoV-2 entering the olfactory bulb. The mechanism of SARS-CoV-2 neuropathogenesis in the olfactory bulb requires a better elucidation and further research studies to mitigate the olfactory bulb damage associated with virus action.

Keywords: COVID-19; SARS-CoV-2; anosmia; neuropathogenesis; olfactory bulb.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Representative lung parenchyma from HE-stained COVID-19 sections showing (A) perivascular chronic lymphocytic inflammation and microthrombi, (B) microthrombi and the presence of hyaline membranes, (C) the presence of giant multinucleated cells, and (D) the exudative phase of diffuse alveolar damage with superimposed bacterial pneumonia. Magnification: ×200.
Figure 2
Figure 2
Representative olfactory bulb from HE-stained COVID-19 sections showing (a) mild and (b) diffuse reactive astrogliosis. Magnification: ×200.
See this image and copyright information in PMC

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