SYDNEY - Spiking Covid-19 cases detected in wastewater have prompted some scientists to ask whether JN.1, the strain driving an explosive winter surge, is selectively targeting peoples’ intestinal tracts.

The evidence is extremely limited and theoretical, and there is no data suggesting that more people are experiencing severe digestive illnesses from Covid-19.

Yet there is no question that the coronavirus has changed its requirements for entering cells, said Sydney virologist Stuart Turville. This may be consistent with more efficient infection of particular tissues, including the gut.

It is just one of the many debates swirling around JN.1. The variant is so highly infectious and immune evasive that some scientists believe it needs its own Greek name to separate it from its highly infectious progenitor, Omicron.

“Its mode of entry has diverged significantly from what we saw in 2020,” said Associate Professor Turville, whose University of New South Wales lab has been tracking viral entry pathways since the start of the pandemic. “It’s presently the peak of this trajectory.”

JN.1 is the fastest-growing variant to emerge in the past two years.

The World Health Organisation (WHO) designated it a variant of interest on Dec 19 due to its rapid growth and potential to add to the respiratory virus burden in the Northern Hemisphere. The latest booster formulation should provide good protection against it, according to the organisation. 

The strain emerged in August from the ultra-mutated BA.2.86, or Pirola variant. While Pirola was not especially remarkable, a hallmark mutation that produced JN.1 has resulted in greater transmissibility and immune evasiveness, University of Tokyo scientists reported earlier in December.

JN.1 is accelerating a year-end Covid-19 wave. In the United States, it accounted for up to 29 per cent of the strains in circulation as of Dec 8 – and Covid-19 hospitalisations are rising quickly, the Centres for Disease Control and Prevention said.

It warned that low vaccination rates for Covid-19 and other respiratory bugs could lead to more severe disease and strain on the health system for the rest of winter. 

Detections in wastewater have uniformly and exponentially increased in multiple countries, including Austria, Germany, the Netherlands and Switzerland. 

“People are detecting it in wastewater at as high a rate as they were detecting omicron when it first emerged,” said Dr Kanta Subbarao, director of the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne, who chairs the agency’s technical advisory group on Covid-19 vaccine composition.

“But so far, we’re not seeing a parallel or concomitant increase in hospitalisation. I think we have to watch that space.”

An increase in emergency room visits and other medical-use data will offer clues on the severity of illness JN.1 causes, said Dr Subbarao, who is also a professor of microbiology and immunology at the University of Melbourne’s Peter Doherty Institute for Infection and Immunity. “Whether it’s become more gut-associated, for instance, we don’t know,” she said.

The wastewater findings could reflect high circulation in communities, rather than more frequent or more intense gut infections that result in greater or prolonged shedding of the coronavirus in stool.

Diarrhoea was not more frequently reported by Covid-19 sufferers as of November in the Netherlands, which has tracked symptom data since 2020. 

The coronavirus has long shown that it is adept at infecting the gut. The trend away from lower lung infections has been observed since Omicron supplanted the Delta variant in late 2021.

Assoc Prof Turville’s research provides a plausible explanation for the change and why JN.1 might prefer the GI tract, said Mr Ryan Hisner, an Indiana school teacher whose self-taught genomic sleuthing has identified important changes in the pandemic virus’ evolution. 

Still, “it’s not clear”, Mr Hisner said. “We don’t really have any direct evidence.” 

Inherent changes in the virus are difficult to disentangle from the important role vaccinations and prior infections have played in priming the immune system to recognise and attack the virus before it reaches the lungs, he said.

Even if disease patterns are not substantially altered by JN.1, the virus is definitely taking a new pathway into cells, according to Assoc Prof Turville.

While past versions have preferentially latched on to a cleaved version of the ACE-2 cell-surface protein, the new variant represents the coronavirus’s strongest predilection yet for an uncleaved version of the cellular doorway.

“I can’t see it getting any further than JN.1,” Assoc Prof Turville said. “JN.1 is so extreme. The key now is to understand how this translates into what tissue niches it now inhabits.” BLOOMBERG