Preprint: Antigenic & Virological properties of an H3N2 Variant That Will Likely Dominate the 2021-2022 Influenza season

CDC FluView Activity Map - Epi Week 49

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While COVID variants Delta and Omicron are dominating the headlines, seasonal influenza - which was virtually a no show in the 2020-2021 season due to lockdowns, face masks, and social distancing - is showing signs of making a comeback across the nation, and around the world. 

As we've discussed often (see here, here, and here), with so little influenza being reported world-wide since COVID arrived - and many public health departments overwhelmed by the pandemic - we've seen a 99% drop in influenza samples submitted to reference laboratories for analysis.

And that, it was feared, might allow antigenic changes in seasonal flu viruses to go unnoticed, leaving us open to a mismatched flu vaccine whenever influenza finally did return. This potential complication was addressed by the WHO last February, when they announced their 2021-2022 flu vaccine recommendations (Vaccine Q&A document).

18. How has the COVID-19 pandemic impacted the 2021-2022 northern hemisphere influenza vaccine recommendation? 

The volume of data available from recently circulating influenza viruses and the geographic representation have been significantly lower for this northern hemisphere vaccine recommendation meeting than is typical. The reduced number of viruses available for characterization raises uncertainties regarding the full extent of the genetic and antigenic diversity of circulating influenza viruses and those likely to pose a threat in forthcoming seasons. Nevertheless, new groups of A(H3N2) viruses were identified, some of which had spread internationally. Consequently, the A(H3N2) component recommendation has been updated.

We've seen the impact of a `drifted' flu virus before, in 2014 (see CDC HAN Advisory On `Drifted’ H3N2 Seasonal Flu Virus) and again in 2017 (see MMWR: Reviewing Our High Severity 2017-2018 Flu Season), both resulting in overwhelmed hospitals and high morbidity and mortality numbers.

Reports last November of several large outbreaks of influenza at colleges and universities (see here, here, and here) led to a CDC investigation, followed by an MMWR Report, and the issuance of a HAN Advisory # 00458, that described the H3N2 viruses collected as being similar to - but genetically distinct from - this year's H3N2 vaccine component.

Which brings us to a preprint published last week that seems to corroborate those findings. 

BRIEF COMMUNICATION

Antigenic and virological properties of an H3N2 variant that will likely dominate the 2021-2022 Northern Hemisphere influenza season

Marcus J. Bolton1 , Jordan T. Ort1 , Ryan McBride2 , Nicholas J. Swanson3 , Jo Wilson3 , Moses Awofolaju1 , Allison R. Greenplate4 , Elizabeth M. Drapeau1 , Andrew Pekosz3 , James C. Paulson2 , Scott E. Hensley1,*  

Abstract

Influenza viruses have circulated at very low levels during the COVID-19 pandemic, and population immunity against these viruses is low. Influenza virus cases have been increasing in the Northern Hemisphere involving an H3N2 strain (3C.2a1b.2a2) with a hemagglutinin (HA) that has several substitutions relative to the 2021-2022 H3N2 vaccine strain.

 

Here, we show that one of these substitutions eliminates a key glycosylation site on HA and alters sialic acid binding. Using glycan array profiling, we show that the 3C.2a1b.2a2 H3 maintains binding to an extended bi-antennary sialoside and replicates to high titers in human airway cells. We found that antibodies elicited by the 2021-2022 Northern Hemisphere influenza vaccine poorly neutralize the new H3N2 strain. Together, these data indicate that 3C.2a1b.2a2 H3N2 viruses efficiently replicate in human cells and could potentially cause an antigenic mismatch if they continue to circulate at high levels during the 2021-2022 influenza season.

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Even though I was more than aware this could happen, I got my flu shot last September, and I'm glad I did.  Even if it isn't an exact match, it will still likely provide me with some protection, and would likely reduce the severity of illness is I became infected. 

Given what we know - or strongly suspect - about the dangers of COVID and Influenza coinfection (see PHE Study: Co-Infection With COVID-19 & Seasonal Influenza), I'd still strongly recommend getting the flu shot. 

Some additional studies include: 

PLoS NTD: Clinical & Virological Impact of Single and Dual Infections with influenza A (H1N1) and SARS-CoV-2

Nature: Co-infection of SARS-CoV-2 & Influenza Causes More Severe and Prolonged Pneumonia in Hamsters

China CCDC Weekly: Public Health Control Measures for the Cocirculation of Influenza and SARS-CoV-2 During Influenza Seasons

Even without the added complications of COVID, after more than 18 months without influenza exposure, our community immunity to influenza is likely low, and this year's early sampling of flu viruses indicates that H3N2 - which is often linked to more severe flu seasons - is the most common subtype detected.

Since hospitals and emergency services are likely to experience heavy demand in the months ahead (see More U.S. Hospitals Inch Towards Invoking Crisis Standards of Care), and the links between influenza infection and heart attacks and strokes continue to grow, anything you can do to avoid needing a hospital bed in the months ahead is a good investment. 

While individually, the COVID vaccine (and booster), the flu vaccine, the wearing of face masks, and social distancing may provide less-than-perfect protection against infection or illness - when combined - they can substantially reduce your risk. 

And right now, that's the best game in town.