SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs
Marco Dell’Aquila,
Concetta Cafiero,
Alessandra Micera,
Egidio Stigliano,
Maria Pia Ottaiano,
Giulio Benincasa,
Beniamino Schiavone,
Leo Guidobaldi,
Luigi Santacroce,
Salvatore Pisconti,
Vincenzo Arena,
Raffaele Palmirotta
Affiliations
Marco Dell’Aquila
Anatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Concetta Cafiero
Medical Oncology, SG Moscati Hospital, 74010 Statte, Italy
Alessandra Micera
Research and Development Laboratory for Biochemical, Molecular and Cellular Applications in Ophthalmological Science, IRCCS–Fondazione Bietti, 00184 Rome, Italy
Egidio Stigliano
Anatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Maria Pia Ottaiano
Department of Clinical Pathology and Molecular Biology, Pineta Grande Hospital, 81030 Castel Volturno, Italy
Giulio Benincasa
Department of Clinical Pathology and Molecular Biology, Pineta Grande Hospital, 81030 Castel Volturno, Italy
Beniamino Schiavone
Department of Clinical Pathology and Molecular Biology, Pineta Grande Hospital, 81030 Castel Volturno, Italy
Leo Guidobaldi
Cytodiagnostic Unit, Section of Pathology Sandro Pertini Hospital, ASL Rm2, 00157 Rome, Italy
Luigi Santacroce
Section of Microbiology and Virology, Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy
Salvatore Pisconti
Medical Oncology, SG Moscati Hospital, 74010 Statte, Italy
Vincenzo Arena
Anatomic Pathology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Raffaele Palmirotta
Section of Sciences and Technologies of Laboratory Medicine, Interdisciplinary Department of Medicine, School of Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy
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.
