The debut of the pandemic coronavirus wreaked universal havoc – not even seasonal flu viruses were spared. Amid travel restrictions, quarantines, closures, physical distancing, masks, improved hand washing and disinfection, the 2020-2021 flu season was all but cancelled. That meant not only an unprecedented worldwide decline in the number of flu patients, but also a dramatic collapse in the genetic diversity of circulating flu strains. Many subtypes of the virus have all but disappeared. But most notably, one entire lineage — one of only four flu groups targeted by seasonal flu vaccines — went completely dark, seemingly extinct.
Researchers noted the absence last year as the flu still struggled to recover from the pandemic knockout. But now the flu has returned and threatens to set off a particularly nasty season in the Northern Hemisphere. Yet the B/Yamagata lineage is still missing, according to a study published this week in the journal Eurosurveillance. It has not been definitively detected since April 2020. And the question of whether it really went extinct still lingers.
What the absence of B/Yamagata might mean for future flu seasons and flu shots also remains an open question. For a quick refresher, in recent years, four main types of seasonal flu have been circulating among people worldwide. Two are influenza type A viruses: subtypes of H1N1 viruses and H3N2 viruses. The other two are influenza type B viruses: offshoots of the Victoria and Yamagata lines. (For a more detailed explanation of flu, check out our explanation here.) Current quadrivalent vaccines target seasonally specific versions of each of these four types of flu viruses.
With fewer flu viruses around, it may be easier to match future vaccines to circulating viruses, making seasonal injections more effective. On the other hand, a surprising re-emergence of B/Yamagata could become more dangerous as time goes on and people lose their immunity. But before health experts can play out future flu seasons, they’d like to know if B/Yamagata is really gone.
disappeared virus
In an article published this week in the journal Eurosurveillance, researchers in the Netherlands ran through the latest global flu surveillance data through August 31, 2022 in search of the missing strain. They note that GISAID, a global database of influenza virus genetic sequences that typically receives thousands of flu sequences per year, has not received any B/Yamagata sequences containing sample collection data after March 2020.
The World Health Organization’s FluNet surveillance data has had a small number of reports of the missing lineage – 43 in 2021, mostly from China, and eight sporadic cases from four countries in 2022. By comparison, there were more than 51,000 detections of B/Yamagata in the year. 2018.
The authors suggest that the small number of cases in the past two years could be false detections. Instead of putting viruses into circulation, they can simply detect B/Yamagata signatures from vaccines containing live attenuated influenza viruses. Or they could be genetic contamination from inactivated virus vaccines. This is not just hypothetical. The authors note that a number of B/Yamagata detections in the US and Scotland came from live attenuated flu vaccines rather than actual cases of circulating virus.
The researchers are calling for flu surveillance labs to step up their efforts to detect Yamagata cases to determine if it’s really gone or just low. “From a laboratory perspective, we think it would be advisable to increase the ability and capacity to determine the lineage of all influenza B viruses detected around the world, as this is critical to detecting the absence of B/Yamagata. lineage viruses,” they conclude. They also propose that the World Health Organization establish criteria to determine when the lineage can be declared “extinct” and what the consequences of that declaration might be.
