Research on how this coronavirus attacks the olfactory system is beginning to emerge. In July, a team led by Sandeep Robert Datta, a neurobiologist at Harvard, published a paper suggesting that the virus does not directly infect smell-receptor neurons in the nose. Instead, the virus is probably infecting support cells in the olfactory system, which normally help replenish the supply of smell-receptor neurons. COVID-19 infection might interrupt this replenishment, leading to sudden but usually temporary smell loss.
Infection of the support cells may also help explain the parosmia that people find especially distressing. When the smell-receptor neurons do finally regenerate, they have to find their way up the nasal cavity, through tiny holes in the base of the skull, and finally to the right structures in the olfactory bulb. “That is an error-prone process,” Datta told me. Humans have only 400 distinct smell receptors, but can distinguish potentially 1 trillion different odors. That’s because a single molecule can bind to multiple smell receptors, and one recognizable scent can be made up of hundreds of different molecules that together activate a unique combination of receptors. If some receptors are missing or miswired, the brain might get a scrambled signal that results in parosmia. The miswiring normally gets sorted out after several weeks or months.
“But to be honest, I think there are many things about parosmia we simply don’t understand yet that suggest that more complicated things are going on,” Datta said. For one, why are the scents associated with parosmia usually so foul? The exact smell is “impossible to describe,” Kelly said, but people almost always grasp for words that evoke disgust: sewage, rotten, putrid. In parosmia, Hummel hypothesizes that the brain is interpreting unfamiliar, scrambled signals from miswired olfactory neurons as danger. “Why should something you’ve never smelled before be pleasant?” he says. In our evolutionary history, smells like smoke or rot have often acted as warnings.
Strangely enough, though, babies do not seem to have a natural aversion to bad smells. They certainly react to bad tastes or irritants, but they don’t turn their heads away from foul odors. “When they’re very young, their diapers do not disgust them,” Dalton, the psychologist at Monell Chemical Senses Center, notes. The aversion to certain smells seems to be learned over a lifetime, but once we’ve learned it, the reaction is very strong indeed.
The connections among smell, emotion, and memory are apparent in our neurobiology, too. Smell-receptor neurons converge on the olfactory bulb, which then sends signals to be processed by the olfactory cortex. But the olfactory bulb is also connected to the amygdala, which is involved in emotions and memory, and the hippocampus, which is also important in memory. “When you smell something, it drives activity in all these areas, and all of these areas talk to each other,” Datta said. “The way your olfactory cortex understands odors depends at least in part on your memories of the odors.” How a particular scent is represented in the brain remains an unsolved mystery. Neurobiologists are able to quantify visual or audio cues, but mapping the relationship between smells is a lot more complicated. Certain smells are definitely related to one another—lemon and lime seem to activate overlapping sets of neurons in the brain, for instance—but scale that to billions of potentially smellable molecules, and mapping them quickly gets impossible.