What influenza activity can we anticipate in 2022?

We were spared influenza co‐circulating with SARS‐CoV‐2 since 2020, but that is likely to change

Influenza seasons in temperate Australia typically begin in June, peak in August and trail off by October, with some variability from year to year, whereas influenza activity occurs in two periods in the tropical north.1 Since the global spread of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in early 2020, we have not experienced seasonal influenza in Australia; effectively, we were spared influenza circulating concurrently with SARS‐CoV‐2 in 2020 and 2021. Globally, there was virtually no influenza reported after mid‐March in 2020, but influenza activity was reported in 2021 from a few countries (Box, A, C and D), most notably in western Africa and the Indian subcontinent, and the number of cases was small. Several factors, which occurred variably in different countries and even within countries, contributed to the absence of influenza activity during the coronavirus disease 2019 (COVID‐19) pandemic. These included restrictions on international travel; mandatory quarantine for returned travellers; working from home; school closures; social and public health measures, such as mask wearing, physical distancing and hand hygiene; and, potentially, viral interference.2 These factors are not specific to influenza, as evidenced by the fact that the other major seasonal respiratory virus, respiratory syncytial virus, also did not circulate in its normal autumn–winter pattern in Australia in 2020 but re‐emerged in spring 2020 in some states (New South Wales and Western Australia) and in summer 2021 in others (Victoria and Queensland).3

Influenza illness is caused by infection with one of four human influenza viruses: two type A (H1N1pdm09 and H3N2) and two type B (Victoria and Yamagata lineages). During an influenza season, one virus can predominate or two or more of the four viruses can co‐circulate. There is genetic and antigenic heterogeneity within each type, subtype and lineage of viruses, especially among influenza A/H3N2 and, to a lesser extent, influenza A/H1N1pdm09 viruses.

The abrupt cessation of circulation of influenza viruses in 2020 involved all four human influenza viruses. We cannot predict the consequences of such a severe bottleneck on viral evolution — will all of the clades of viruses that were circulating before the COVID‐19 pandemic survive and re‐emerge? Or will only some of the previous clades re‐emerge? This has practical implications for the composition of seasonal influenza vaccines. In 2021, we saw a gradual return of the two influenza A viruses and B/Victoria lineage viruses, but B/Yamagata lineage viruses were not reported (Box) and the genetic heterogeneity within the submitted viruses was reduced from what was seen before the COVID‐19 pandemic. The WHO Collaborating Centre for Reference and Research on Influenza and the larger WHO Global Influenza Surveillance and Response System, of which we are part, are well positioned to conduct genetic and antigenic characterisation of the viruses that emerge and to analyse the consequences of the viral bottlenecks of 2020–2021.

What can we expect in Australia in 2022? With the re‐opening of international borders and lifting of mandatory managed quarantine, we can anticipate the reintroduction of influenza into Australia.4,5 The few influenza notifications in 2021 in Australia (Box, B, inset) were associated with returned travellers who were in hotel quarantine, but these cases did not seed the community because their infectious period had ended before they were released from COVID‐19 quarantine. In contrast, in the last few weeks of 2021, there were notifications of influenza from people who did not have a travel history, suggesting that community transmission of influenza is occurring, although at a very low level. We have a unique opportunity to learn important lessons about the epidemiology of influenza epidemics and pandemics; for example, specifically, at what point does influenza tip over to community spread? How many cases are needed and what is the timeline for the establishment of community outbreaks and epidemics, with or without public health and social measures? Addressing these questions will require timely institution of specific surveillance efforts.

While our primary focus is on seasonal influenza, we must also remain vigilant about zoonotic and pandemic influenza viruses. Although seasonal influenza viruses were in abeyance in 2020–2021, there was widespread influenza virus activity in animals globally and within our own region. Highly pathogenic avian influenza A(H7N7) and low pathogenicity avian influenza A(H7N6) and A(H5N2) viruses6 were reported in Victoria, and swine influenza viruses have been detected in several states.7,8

Human infections can occur in people exposed to animal influenza viruses and such events are monitored by the WHO Global Influenza Surveillance and Response System. In 2021, more than 52 cases of zoonotic influenza virus (avian and swine origin) infections were reported globally.9 The reason for public health concern is that novel (eg, animal) influenza viruses to which the human population lacks immunity could spread to cause a global pandemic if they cross the species barrier to cause human infections and spread efficiently from person to person. Does that sound familiar? We have learnt from COVID‐19 that we ignore the animal–human interface at our own peril. What is needed to be prepared to recognise an influenza virus with pandemic potential? How would we know if a novel virus emerged in Australia? Clearly, an astute clinician or virologist could sound the alarm and investigate clusters of cases such as severe influenza‐like illness within or outside the normal influenza season or a history of exposure to animals. But we can do more to ensure that we detect such events:

1. ▪ we must establish surveillance at the animal–human interface because focusing on viruses that can cross the species barrier is an excellent place to start;
2. ▪ we must invest in subtyping more influenza A viruses than we do (Box, B) because being unable to subtype as H1 or H3 may be the only indication that an animal virus has infected a human;10
3. ▪ we must improve communications between animal and human public health sectors so that we can institute active surveillance in people involved in culling large numbers of infected animals; and
4. ▪ we must work in public–private partnerships to lower the barriers to surveillance at the animal–human interface.

Such efforts will be beneficial beyond influenza: the COVID‐19 pandemic11 and recent reports of a new genotype of Hendra virus in Australian flying foxes12 are excellent reminders that other animal viruses that can cross species barriers bear watching.

Box – Circulation of influenza viruses reported to the WHO Global Influenza Surveillance and Response System in 2020 and 2021

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Number of specimens positive for influenza by subtype. (A) Global data 2020–2021. (B) Australia 2020–2021, with an inset of activity reported in 2021. (C) Northern hemisphere 2021. (D) Southern hemisphere 2021. Note the scale on the y axes. Orange shows influenza B: lightest shade, B Yamagata lineage; medium shade, B Victoria lineage; and darkest shade, B lineage not determined. Blue shows influenza A: lightest shade, A/H1N1pdm09; medium shade, A/H3N2; and darkest shade, influenza A not subtyped. Data source: WHO Global Influenza Surveillance and Response System. https://www.who.int/tools/flunet.