Visualizing in deceased COVID-19 patients how SARS-CoV-2 attacks the respiratory and olfactory mucosae but spares the olfactory bulb

• Published in: Cell 2021-11, Vol.184 (24), p.5932-5949.e15
• Main Authors: Khan, Mona, Yoo, Seung-Jun, Clijsters, Marnick, Backaert, Wout, Vanstapel, Arno, Speleman, Kato, Lietaer, Charlotte, Choi, Sumin, Hether, Tyler D., Marcelis, Lukas, Nam, Andrew, Pan, Liuliu, Reeves, Jason W., Van Bulck, Pauline, Zhou, Hai, Bourgeois, Marc, Debaveye, Yves, De Munter, Paul, Gunst, Jan, Jorissen, Mark, Lagrou, Katrien, Lorent, Natalie, Neyrinck, Arne, Peetermans, Marijke, Thal, Dietmar Rudolf, Vandenbriele, Christophe, Wauters, Joost, Mombaerts, Peter, Van Gerven, Laura
• Format: Article
• Language: English
• Subjects: Aged; Anosmia; Autopsy - methods; B.1.1.7; coronavirus; COVID-19; COVID-19 - mortality; COVID-19 - physiopathology; COVID-19 - virology; Endoscopy - methods; Female; Glucuronosyltransferase - biosynthesis; Humans; Immunohistochemistry; In Situ Hybridization; leptomeninges; Male; Microscopy, Fluorescence; Middle Aged; Olfaction Disorders; olfactory bulb; Olfactory Bulb - virology; Olfactory Mucosa - virology; olfactory receptor; Olfactory Receptor Neurons - metabolism; olfactory sensory neuron; Respiratory Mucosa - virology; Respiratory System; SARS-CoV-2; Smell; sustentacular cell; UGT2A1
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2021.10.027

Anosmia, the loss of smell, is a common and often the sole symptom of COVID-19. The onset of the sequence of pathobiological events leading to olfactory dysfunction remains obscure. Here, we have developed a postmortem bedside surgical procedure to harvest endoscopically samples of respiratory and olfactory mucosae and whole olfactory bulbs. Our cohort of 85 cases included COVID-19 patients who died a few days after infection with SARS-CoV-2, enabling us to catch the virus while it was still replicating. We found that sustentacular cells are the major target cell type in the olfactory mucosa. We failed to find evidence for infection of olfactory sensory neurons, and the parenchyma of the olfactory bulb is spared as well. Thus, SARS-CoV-2 does not appear to be a neurotropic virus. We postulate that transient insufficient support from sustentacular cells triggers transient olfactory dysfunction in COVID-19. Olfactory sensory neurons would become affected without getting infected. [Display omitted] •A postmortem bedside surgical procedure was developed for COVID-19 and control patients•Ciliated cells are the main target cell type for SARS-CoV-2 in the respiratory mucosa•Sustentacular cells (non-neuronal) are the main target cell type in the olfactory mucosa•No evidence for infection of olfactory sensory neurons or olfactory bulb parenchyma Postmortem samples of respiratory and olfactory mucosa and whole olfactory bulbs are harvested immediately after the death of COVID-19 patients revealing ciliated cells and sustentacular cells but not olfactory sensory neurons as the main target cell types for SARS-CoV-2 infection and replication.