Persistent COVID-19 raises 2022 "Twindemic" potential as flu season arrives

Before COVID-19, the infectious disease that accounted for a large majority of deaths among insured populations in Europe and the Americas had been rapidly spreading seasonal flu or influenza. It is estimated that amongst the up to 1 billion global influenza infections, there are between 290,000 and 650,000 deaths each year [1]. With many questions still open about how the new Omicron SARS-CoV-2 variant will impact the severity of COVID-19 infections this winter, a flu-COVID "twindemic" returns as a distinct possibility.

Here, we examine past trends, as well as the outlook for the 2022 seasonal flu in some major markets.

The facts on the flu

Flu is the generic disease that encompasses respiratory illnesses caused by influenza viruses and their different strains. Seasonal flu infections typically occur in the autumn and winter months of the respective hemispheres, though infections can occur throughout the year in tropical regions. In the US, UK and Canada, the flu season typically begins in October and peaks in January or February, whereas in Australia, the season starts in May and hits its zenith in August. According to the World Health Organization (WHO), the spread of influenza has been seen from southern-to-northern countries 2.

Compared to the virus that causes COVID-19, influenza has a notably higher mutation rate 3. Flu outbreaks happen annually as influenza viruses undergo constant genetic change, which can cause new strains to circulate each year that are less recognizable to the body's immune system. For instance, scientists believe significant changes in a flu virus helped drive the deadly influenza pandemic that killed millions worldwide in1918.

Several other factors known to influence the severity of seasonal flu include immunity levels, severity of the effects of the particular flu viruses in circulation, flu vaccination uptake and opportunities within groups of people or societies for the virus to be transmitted.

Why is this flu season different in the context of COVID-19?

Despite the previous flu season's apparent mildness, circumstances unique to living during a pandemic still have the potential to exacerbate the severity of the 2021-22 flu season. The relatively limited influenza circulation during the past two seasons may have left fewer people exposed to influenza's various strains to maintain historic levels of immunity. We also face an evolving situation in which many countries are easing public health measures, allowing for significantly more social interaction - potentially without protective measures in place - as the number of people who have been vaccinated against COVID-19 grows and populations grow weary of restrictions. Population immunity and protection against influenza may therefore be reduced this season, resulting in a concerning health scenario in which influenza and COVID-19 can co-circulate.  

Such a "twindemic" could have major consequences for people most vulnerable to influenza and COVID-19, including older adults, those with underlying health conditions and pregnant women 11,12. Simultaneous flu and COVID-19 viral infections are also possible, with one study finding the likelihood of co-infection and ICU admission increased with age among COVID-19 patients 13. A second study on mice found pre-infection with Influenza A virus increased the likelihood of subsequent infectivity and viral load of SARS-CoV-2 14.  

Surges of both illnesses could also overwhelm healthcare systems, just as rising infections with the COVID-19 Delta variant added to burdens on hospital ICU beds and equipment resources in Europe and the Americas. Public Health England has referenced one study that predicted a 50% increase in influenza this season for the UK 15. A similar scenario, were it to occur on other geographies, could mean an additional 17,500, 3,000 and 2,000 influenza-associated deaths in the US, Canada, and the UK, respectively. This would come atop deaths attributable to COVID-19, which are already projected to increase in December 2021 and for much of January 2022 in these countries 16. More research is still needed, however, to fully comprehend the risks associated with co-infection and co-circulation, given the absence of real-world evidence.

Will flu vaccinations help?

Flu vaccinations remain the best form of protection against severe illness and death from the flu. Even while the effectiveness of flu vaccines tends to range between 40-60%, this provides a significant amount of protection against the worst consequences of severe disease, given how many people contract the flu during a typical flu season who may require medical assistance 17. One study estimated that 105,000 hospitalizations and 6,300 deaths were prevented in the US with the flu vaccine in the 2019-20 flu season 18.

Some agencies including the CDC and the European Commission have been reinforcing the importance of influenza vaccination efforts, in hopes of reducing simultaneous infections and hospitalizations from influenza and COVID-19.  This comes against the backdrop of concerns that general vaccine fatigue or hesitancy may be growing in the wake of the existing push for COVID-19 vaccinations, which includes inoculation mandates being introduced in some countries. Europe has also raised concerns about "considerable differences" in uptake of flu vaccines between EU member countries, with some at nearly 70% of their older patients, and others at less than 10%.

According to an initial clinical trial, it has been deemed safe to administer flu jabs concurrently with COVID-19 vaccines (Pfizer and AstraZeneca) 19. It is also possible that manufacturers will consider producing a combination flu-COVID vaccine to maximize the number of people who protect themselves against both diseases in a single sitting. 

What can we expect in future flu seasons?

While the restrictions and behavioral changes made in response to COVID-19 temporarily reduced the impact of the 2020-21 flu season, this relief may be unlikely to persist much beyond 2021 – if that. However, we can now imagine scenarios where the impact of seasonal flu is reduced overall if improved personal and community protective measures become ingrained in society. Vaccine manufacturers may also combine the flu vaccine with a COVID vaccine in the future, and this may increase the uptake. Finally, as COVID becomes endemic, flu mortality may be reduced by virtue of having a competing virus in circulation that affects the same vulnerable population as flu – i.e., the elderly and those with co-morbidities. 


 3SARS-CoV-2 and influenza: a comparative overview and treatment implications | Boletín Médico del Hospital Infantil de México (
6Your Data - Nomis - Official Labour Market Statistics (
7Causes of Death, Australia | Australian Bureau of Statistics (
9Review of global influenza circulation, late 2019 to 2020, and the impact of the COVID-19 pandemic on influenza circulation (
10Similarities and Differences between Flu and COVID-19 | CDC
11COVID-19 Information for Specific Groups of People | CDC
12People at Higher Risk of Flu Complications | CDC
13Influenza co-infection associated with severity and mortality in COVID-19 patients | Virology Journal | Full Text (
14Coinfection with influenza A virus enhances SARS-CoV-2 infectivity | Cell Research (
15National flu immunisation programme 2021 to 2022 letter - GOV.UK (
16COVID-19 (
17CDC Seasonal Flu Vaccine Effectiveness Studies | CDC
18Estimated Influenza Illnesses, Medical visits, and Hospitalizations Averted by Vaccination in the United States — 2019–2020 Influenza Season | CDC
19September: comfluvcov-study | News and features | University of Bristol



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