COVID may have pushed a leading seasonal flu strain to extinction


A bottle of influenza vaccine at a CVS pharmacy and MinuteClinic on September 10, 2021, in Miami.
Enlarge / A bottle of influenza vaccine at a CVS pharmacy and MinuteClinic on September 10, 2021, in Miami.

The pandemic coronavirus’ debut wrought universal havoc—not even seasonal flu viruses were spared. Amid travel restrictions, quarantines, closures, physical distancing, masking, enhanced hand washing, and disinfection, the 2020-2021 flu season was all but canceled. That meant not just an unprecedented global decrease in the number of people sick with the flu but also a dramatic collapse in the genetic diversity of circulating flu strains. Many subtypes of the virus all but vanished. But most notably, one entire lineage—one of only four flu groups targeted by seasonal influenza vaccines—went completely dark, seemingly extinct.

Researchers noted the absence last year as the flu was still struggling to recover from its pandemic knockout. But now, the flu has come roaring back and threatens to cause a particularly nasty season in the Northern Hemisphere. Still, the influenza B/Yamagata lineage remains 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’s truly gone extinct lingers.

What B/Yamagata’s absence might mean for future flu seasons and flu shots also remains an open question. For a quick refresher: Four main types of seasonal flu have been circulating globally among humans in recent years. 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 lineages. (For a more detailed explanation of influenza, check out our explainer here.) Current quadrivalent vaccines target season-specific versions of each of these four types of flu viruses.

Having fewer flu viruses around means it could be easier to match future vaccines to circulating viruses, making seasonal shots more effective. On the other hand, a surprise re-emergence of B/Yamagata could become more dangerous as time passes and people lose immunity. But, before health experts can game out future influenza seasons, they’d like to know if B/Yamagata is truly gone.

Vanished virus

In an article published this week in the journal Eurosurveillance, researchers in the Netherlands sifted through the latest global influenza surveillance data up to August 31, 2022, looking for the missing strain. They note that GISAID, a global database of influenza virus genetic sequences that typically gets thousands of flu sequences each year, has not received a single B/Yamagata sequence with specimen 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. For comparison, there were more than 51,000 detections of B/Yamagata in 2018.

The authors suggest the small number of cases in the last two years may be erroneous detections. Rather than circulating viruses, they may simply be detecting signatures of B/Yamagata from vaccines that carry live-attenuated influenza viruses. Or, they could be genetic contamination from inactivated-virus vaccines. This isn’t just a hypothetical. The authors note that a number of B/Yamagata detections in the US and Scotland were found to be from live-attenuated influenza vaccines rather than real cases of circulating virus.

The researchers call for flu surveillance laboratories to increase efforts to detect any Yamagata cases to determine if it’s truly gone or just lying low. “From a laboratory perspective, we think it would be advisable to increase the capability and capacity to determine the lineage of all detected influenza B viruses around the world as this is critical to determine the absence of B/Yamagata lineage viruses,” they conclude. They also propose that the World Health Organization set up criteria to define when the lineage could be declared “extinct” and what the consequences of what that declaration might be.