Examination of human brain tissue has presented inconsistent findings. While some studies have detected the presence of SARS-CoV-2, others have only located evidence of inflammatory damage.
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Animal models suggest that it is plausible for the virus to infect the brain; however, since human tissue samples are obtained postmortem, researchers can merely speculate on what transpires during an active infection.
In a new study, conducted by scientists at Institut Pasteur and Université Paris Cité, an animal model was utilized to explore several unresolved questions.
Specifically, the research focussed on how SARS-CoV-2 could enter the brain via the olfactory system, whether different SARS-CoV-2 variants are more or less likely to enter the brain, and if loss of smell is directly linked to virus entering the brain.
Using hamsters as a model organism, infection with the original SARS-CoV-2 virus from 2020 as well as subsequent variants including Gamma, Delta and Omicron/BA.1 were compared.
The results confirmed epidemiological observations that acute disease severity is reduced in Omicron infections. However, all variants showed similar neuroinvasive capabilities and intriguingly infected the brain’s olfactory regions regardless of whether symptoms of anosmia (loss of sense of smell) were present or not.
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“This suggests that anosmia and neuronal infection are two unrelated phenomena,” says first author 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.”
The researchers utilized a modeling system called microfluidic cell culture to gain an in-depth understanding of how SARS-CoV-2 could infect brain cells. This system enabled them to observe the virus and its potential to move between neurons via axons, which are small projections between the cells. The results showed that the virus was able to traverse these connections.
“The virus seems to effectively exploit the physiological mechanisms of the neuron to move in both directions,” explained Dias de Melo. “The SARS-CoV-2 variants we studied – the ancestral Wuhan variant, Gamma, Delta and Omicron/BA.1 – infect neurons in vitro and are capable of moving along axons.”
“The next step will be to understand, from the animal model, whether the virus is able to persist in the brain beyond the acute phase of infection, and whether the presence of the virus can induce persistent inflammation and the symptoms described in cases of long COVID, such as anxiety, depression and brain fog,” said Bourhy.
