In this study, researchers from the Ins ut Pasteur and Université Paris Cité have demonstrated, in an animal model, that a panel of SARS-CoV-2 variants of interest (the original strain of the virus first detected in Wuhan and the gamma, delta and omicron/BA.1 variants) can enter the central nervous system and remain there during the acute phase of the infection.
The researchers observed that all these variants spread to the central nervous system and infect the olfactory bulb, a structure located in the cranial cavity that processes olfactory information before transmitting it to the cortex.
"In this study, we demonstrated that infection of the olfactory bulb is common to all variants and not linked to any particular one, nor to any particular clinical manifestation such as anosmia," explains Guilherme Dias de Melo, first author of the study and researcher in the Ins ut Pasteur's Lyssavirus, Epidemiology and Neuropathology Unit.
Moreover, the researchers identified a genetic sequence linked to anosmia in the ancestral (Wuhan) virus. When this genetic sequence, which encodes the ORF7ab protein, is deleted or truncated—which is the case in certain variants less likely to produce anosmia—the incidence of olfactory loss in infected animals is lower even though the degree of neuronal infection via the olfactory bulbs remains unchanged.
"This suggests that anosmia and neuronal infection are two unrelated phenomena," says Guilherme Dias de Melo. "If we follow this line of reasoning, it is quite possible that even an asymptomatic—and therefore clinically benign—infection is characterized by the spread of the virus in the nervous system."