New research on the Omicron subvariant of the coronavirus has suggested the pathogen could be changing how it attacks the human body – shifting from infecting respiratory systems to increasingly targeting the brain. Researchers from Australia and France found BA.5 – the coronavirus subvariant driving what is now the world’s biggest surge of infections in China – did much more severe damage to mouse brains and cultured human brain tissues than the previous BA.1 subvariant, leading to brain inflammation, weight loss and death. The findings challenge the common belief that viruses usually evolve to become less pathogenic. “Compared with BA. 1, we found that a BA.5 isolate displayed increased pathogenicity in K18-hACE2 mice with rapid weight loss, brain infection and encephalitis, and mortality. In addition, BA.5 productively infected human brain organoids significantly better than BA. 1,” a manuscript of the research said. The manuscript has been uploaded to the preprint platform bioRxiv, and will receive peer review for publication. “These results suggest that the Omicron lineage is not evolving towards reduced pathogenicity,” wrote the team, which was led by virologist Andreas Suhrbier from the QIMR Berghofer Medical Research Institute in Queensland, Australia. Covid-19 outbreaks test China’s position at centre of global supply chain However, other experts have sounded a note of caution, noting that a major limitation of the study was the mouse model it had used, which they said probably did not apply to human beings. “They showed that all the mice died from brain infections of BA. 5, which is apparently very different from human infections that we know of,” said Jin Dongyan, a virologist at the University of Hong Kong. Jin said it was widely accepted that BA.5 did not cause more brain abnormalities in humans than previous subvariants, adding that the World Health Organization has said the pathogenicity of Omicron variants has not increased. In a paper published in the journal Nature last month, a team of Japanese and US scientists reported that BA.5 seemed to have inherited the reduced pathogenicity of Omicron subvariants. Multiple studies have shown that BA.5 is more transmissible than other Omicron subvariants and can evade a human immune system with a previous Covid-19 vaccination or infection. The strain has been detected in more than 100 nations and was the dominant strain in countries such as the United States and the United Kingdom a few months ago. In China, the two major strains circulating are BA. 5.2 and BF. 7, both sub-lineages of BA.5 . Together they accounted for more than 80 per cent of the country’s total Covid-19 infections, said Xu Wenbo, director of the National Institute for Viral Disease Control and Prevention, on Tuesday. There was well documented evidence for brain abnormalities and infection among Covid-19 patients, Suhrbier and his team wrote. To conduct the study, the researchers used a type of transgenic mice known as K18-hACE2, which have been widely used in Covid-related research. The team found the virus likely entered mouse brains via the olfactory epithelium, a special tissue inside the nasal cavity related to sensing smell. China shifts Covid focus to critical care with push for more beds Screening results showed widespread infection of neurons in the cortex of BA. 5-infected mice, as well as the hippocampus and hypothalamus deep in the brain. All those mice suffered weight loss of more than 20 per cent within five days of infection, and were later euthanised. In contrast, similar levels of weight loss only happened to one-fifth of the mice infected with BA.1. Most of the BA. 1-infected mice showed no symptoms, with no virus detected in their brains. The authors said more work was needed to better understand the neuroinvasive mechanism. However, even if respiratory disease is less severe for Omicron variants as a whole, BA.5 may show increased risk of acute and long term neurological complications over previous Omicron variants. Still, critics maintain there is a big gap between studies using the mouse model and those using humans. “After all, the pathogenicity that matters is the pathogenicity to human patients, not to mice,” Jin said.
