US researchers have found the mechanism behind the loss of smell among people infected with Covid-19. The study may also shed light on the effects of Covid-19 on other types of brain cells, and on other lingering neurological effects of Covid-19 like "brain fog", headaches, and depression.
Researchers from NYU Grossman School of Medicine and Columbia University found that infection with SARS-CoV-2 indirectly dials down the action of olfactory receptors (OR), proteins on the surfaces of nerve cells in the nose that detect the molecules associated with odours.
Experiments showed that the presence of the virus near nerve cells (neurons) in olfactory tissue brought an inrushing of immune cells, microglia and T cells, that sense and counter infection.
Such cells release proteins called cytokines that changed the genetic activity of olfactory nerve cells, even though the virus cannot infect them, the researchers said.
"Our findings provide the first mechanistic explanation of smell loss in Covid-19 and how this may underlie long Covid-19 biology," said Benjamin, Professor in the Department of Microbiology at NYU Langone Health.
"The work also suggests how the pandemic virus, which infects less than 1 per cent of cells in the human body, can cause such severe damage in so many organs," he added.
One unique symptom of Covid-19 infection is loss of smell without the stuffy nose seen with other infections like the common cold, researchers said.
In most cases, the smell loss lasts only a few weeks, but for more than 12 per cent of Covid-19 patients, olfactory dysfunction persists in the form of ongoing reduction in the ability to smell (hyposmia) or changes in how a person perceives the same smell (parosmia).
To gain insight into Covid-19-induced smell loss, the team explored the molecular consequences of SARS-CoV-2 infection in golden hamsters and in olfactory tissue taken from 23 human autopsies.
The experiments confirmed that SARS-CoV-2 infection, and the immune reaction to it, decreases the ability of DNA chains in chromosomes that influence the formation of olfactory receptor building to be open and active, and to loop around to activate gene expression.A
In both hamster and human olfactory neuronal tissue, the research team detected persistent and widespread downregulation of olfactory receptor building.
Further, the experiments in hamsters recorded over time revealed that downregulation of olfactory neuron receptors persisted after short-term changes that might affect the sense of smell had naturally recovered.
This suggests that Covid-19 causes longer-lasting disruption in chromosomal regulation of gene expression, representing a form of "nuclear memory" that could prevent the restoration of OR transcription even after SARS-CoV-2 is cleared.
In the next step, the team is looking into whether treating hamsters with long Covid with steroids can restrain damaging immune reactions (inflammation) to protect nuclear architecture.
