COVID may have driven a major seasonal flu strain to extinction

Enlarge / A flu vaccine vial at a CVS and MinuteClinic pharmacy on September 10, 2021 in Miami. Getty | Joe Raedle

The early days of the pandemic coronavirus wreaked universal havoc: even seasonal flu viruses were not spared. Amid travel restrictions, quarantines, shutdowns, physical distancing, masking, enhanced handwashing and sanitizing, the 2020-2021 flu season has been all but cancelled. This meant not only an unprecedented global decrease in the number of people with influenza, but also a dramatic collapse in the genetic diversity of circulating influenza strains. Many subtypes of the virus have virtually disappeared. But most notably, an entire lineage—one of only four flu groups targeted by seasonal flu vaccines—turned completely black, seemingly extinct.

Researchers noted the absence last year when the flu was still struggling to recover from its pandemic knockout. But now the flu is back in full force and threatens to bring about a particularly nasty season in the northern hemisphere. However, the influenza B/Yamagata lineage remains missing, according to a study published this week in the journal Eurosurveillance. It has not been definitely detected since April 2020. And the question of whether it really disappeared persists.

What the absence of B/Yamagata might mean for future flu seasons and flu vaccines also remains an open question. For a quick refresher: Four main types of seasonal flu have circulated around the world among humans in recent years. Two are type A influenza viruses: the H1N1 virus and H3N2 virus subtypes. The other two are type B influenza viruses: offspring of the Victoria and Yamagata lineages. (For a more detailed explanation of influenza, see our explainer here.) Current quadrivalent vaccines target season-specific versions of each of these four types of influenza virus.

Having fewer flu viruses 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 their immunity. But, before health experts can determine future flu seasons, they'd like to know if B/Yamagata is really gone.

Virus disappeared

In an article published this week in the journal Eurosurveillance, Dutch researchers sifted through the latest global flu surveillance data up to August 31, 2022, looking for the missing strain. They note that GISAID, a global influenza virus genetic sequence database that typically receives thousands of influenza sequences each year, did not receive a single B/Yamagata sequence with sample collection data after March 2020.

World Health Organization FluNet surveillance data has had a small number of missing lineage reports: 43 in 2021, mostly from China, and eight sporadic cases in four countries in 2022. As By comparison, there were over 51,000 B/Yamagata detections in 2018.

The authors suggest that the small number of cases over the past two years could be a misdetection. Rather than circulating viruses, they can simply detect signatures of B/Yamagata from vaccines carrying live attenuated influenza viruses. Or, it could be genetic contamination from inactivated virus vaccines. It's not just a hypothesis. The authors note that a number of detections of B/Yamagata in the United States and Scotland were from live attenuated influenza vaccines rather than actual cases of circulating virus.

Researchers are calling on flu-monitoring labs to increase their efforts to detect any cases of Yamagata to determine if it is truly gone or just declining. “From a laboratory perspective, we believe it would be desirable to increase the capacity and ability to determine the lineage of all influenza B viruses detected worldwide, as this is essential to determine the absence of B/Yamagata lineage virus,...