Newer coronavirus variants are less infectious to brain

The omicron BA.1 variant of SARS-CoV-2 is less infectious in the brain and triggers less inflammation in brain cells than the virus variant responsible for the first SARS-CoV-2 wave. This has been shown in research with hamsters and human brain cells by scientists from the Erasmus MC. ‘Good news, but no guarantees for the future.’

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Human stem cell derived brain cells (red and blue) infected with infected with the D614G SARS-CoV-2 (green) ancestral strain.

Loss of smell, concentration problems and brain fog: infection with SARS-CoV-2 can cause all sorts of neurological problems. But there are differences among the SARS-CoV-2 variants. In particular, loss of smell seems to occur less often after infection with Omicron BA.1.

Scientists at the departments Viroscience and Psychiatry from at Erasmus MC have shown that the Omicron BA.1 and Delta variants do indeed infect the brain less efficient compared to the coronavirus variant that caused the first wave in the Netherlands, called D614G. They publish their research in Acta Neuropathologica Communications.

Olfactory bulb

The researchers infected groups of four hamsters with the three virus variants. After five days, they analyzed how much virus and inflammation was present in the hamsters’ nose, olfactory bulb and other parts of the brain. Previous research showed that the SARS-CoV-2 can enter the brain via the olfactory nerve. The researchers used hamsters as a model, because the pathophysiology of the coronavirus infection in these animals resembles that of humans.

In the hamsters infected with the Omicron BA.1 or Delta variants, the virus was found in the nose, but no infected cells could be detected in the brain. This suggests that Omicron BA.1 or Delta did not enter the brain via the olfactory nerve. In hamsters infected with the D614G virus variant, it did, and the scientists detected inflammation in the in the olfactory bulb. This may explain—in part—the loss of smell in patients. In other parts of the brain, virus or inflammation could not be detected.

In human inducible pluripotent brain stem cells, the researchers found the same differences. Omicron BA.1 and Delta were less able to infect the brain cells and did not trigger an inflammatory response compared to the D614G variant.

No guarantees

What can explain these differences? According to the researchers, they are likely the result of the same mutations that make new virus variants less pathogenic. ‘All viruses evolve over time and with that comes different phenotypic characteristics. This seems to be good news concerning the effects on the brain, but I cannot give any guarantees for future virus variants. The evolution of this virus remains difficult to predict,’ says research leader and virologist Dr. Debby van Riel.

What an infection with the coronavirus does to the brain in the long term is not clear from this research. ‘We have looked at the first five days after infection, but we also want to know what happens in the long term. For example, how long does the inflammatory reaction last and can that explain the neurological symptoms of people with long covid? We’d like to find out’, says virologist and researcher Dr. Lisa Bauer.

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