Few of COVID-19’s peculiarities have piqued as much interest as anosmia, the abrupt loss of smell that has become a well-known hallmark of the disease. COVID patients lose this sense even without a stuffy nose; the loss can make food taste like cardboard and coffee smell noxious, occasionally persisting after other symptoms have resolved.

Scientists are now beginning to unravel the biological mechanisms, which have been something of a mystery: The neurons that detect odors lack the receptors that the coronavirus uses to enter cells, prompting a long debate about whether they can be infected at all.

Insights gleaned from new research could shed new light on how the coronavirus might affect other types of brain cells, leading to conditions like “brain fog,” and possibly help explain the biological mechanisms behind long COVID — symptoms that linger for weeks or months after the initial infection.

The new work, along with earlier studies, settles the debate over whether the coronavirus infects the nerve cells that detect odors: It does not. But the virus does attack other supporting cells that line the nasal cavity, the researchers found.

The infected cells shed virus and die, while immune cells flood the region to fight the virus. The subsequent inflammation wreaks havoc on smell receptors, proteins on the surface of the nerve cells in the nose that detect and transmit information about odors.

The process alters the sophisticated organization of genes in those neurons, essentially short-circuiting them, the researchers reported.

Their paper significantly advances the understanding of how cells critical to the sense of smell are affected by the virus, despite the fact that they are not directly infected, said Dr. Sandeep Robert Datta, an associate professor of neurobiology at Harvard Medical School, who was not involved in the study.

“It’s clear that indirectly, if you affect the support cells in the nose, lots of bad things happen,” Datta said. “The inflammation in the adjacent cells triggers changes in the sensory neurons that prevent them from working properly.”

Indeed, many complications of COVID appear to be caused by the immune system’s friendly fire as it responds to infection by flooding the bloodstream with inflammatory proteins called cytokines.