COVID-19, cilia, and smell

Abstract

The novel coronavirus SARS-CoV-2 is the causative agent of the global coronavirus disease 2019 (COVID-19) outbreak. In addition to pneumonia, other COVID-19-associated symptoms have been reported, including loss of smell (anosmia). However, the connection between infection with coronavirus and anosmia remains enigmatic. It has been reported that defects in olfactory cilia lead to anosmia. In this Viewpoint, we summarize transmission electron microscopic studies of cilia in virus-infected cells. In the human nasal epithelium, coronavirus infects the ciliated cells and causes deciliation. Research has shown that viruses such as influenza and Sendai attach to the ciliary membrane. The Sendai virus enters cilia by fusing its viral membrane with the ciliary membrane. A recent study on SARS-CoV-2-human protein-protein interactions revealed that the viral nonstructural protein Nsp13 interacts with the centrosome components, providing a potential molecular link. The mucociliary escalator removes inhaled pathogenic particles and functions as the first line of protection mechanism against viral infection in the human airway. Thus, future investigation into the virus-cilium interface will help further the battle against COVID-19.

Keywords: COVID-19; SARS-CoV-2; cilia; smell loss.

Fig. 1

(A) Left: The electron microscopy image from Ref. [16] shows the sunk cilium and basal body (horizontal arrow) in a ciliated human nasal epithelial cell. The neighbor basal bodies remain at original places (vertical arrows). Scale bar: 1 μm. Middle: schematic diagram of the primary cilium. Right: schematic diagram of the sunk cilium and basal body. (B) Loss and regeneration of cilia during virus infection. (C) Left: Influenza viruses attach to the cilia of trachea epithelial cells (arrows) [23]. Scale bar: 100 nm. Middle: Coronaviruses attach to the cilia (arrows) and microvilli (arrowheads) of nasal epithelial cells [16]. Scale bar: 1 μm. Right: diagram of cilia and microvilli with virus particles attached. (D) Left: Sendai viruses adhere to the cilia of trachea epithelial cells [23]. Some viruses fuse the viral membrane with the cilia membrane, and the nucleocapsids enter the cilia (arrows). Scale bar: 500 nm. Right: A diagram shows that viruses attach to and fuse with the cilia membrane. (E) The Nsp13 protein in SARS‐CoV‐2 interacts with the centrosome proteins [24]. Figure reproduced from Ref. [16, 23].