News & Views: Influenza Season 2021-2022 — Do We Know What to Expect?

Do we know what to expect for the influenza 2021-2022 season? The short answer is no. After all, do we ever know what to expect during influenza season? But this year’s predictability is complicated by the ongoing circulation of SARS-CoV-2, the virus that causes COVID-19. So, let’s take a look at what factors to consider, what to watch for and how to prepare.

2019-2020 and 2020-2021 influenza experiences

The World Health Organization (WHO) recently released their report on influenza from late 2019 through 2020, and the Centers for Disease Control and Prevention (CDC) also released information in anticipation of the upcoming season. Key takeaways included:

• Influenza positivity rates during the 2020-2021 season were significantly lower than typical. In the U.S., while weekly laboratory testing positivity rates are normally between 26% and 30% during influenza season, last year (2020-2021), only about 0.2% of weekly samples were positive for influenza.
• Globally, about two-thirds of cases between November 2019 and December 2020 were influenza type A. The most active period during this time was from late January through early April 2020. During this active period, about 54% of cases in the U.S. and 57% of cases in Canada were influenza A, with the A(H1N1)pdm09 strain predominant in subtyped samples. Type B-subtyped samples detected in the northern hemisphere were almost exclusively of the B/Victoria lineage (98%). 
• An early start (in late October 2019) and late ending (in April 2020) led to an overall longer 2019-2020 influenza season, which, unlike typical seasons, included a third peak in mid-March. Typically, two peaks represent wider circulation of type A early followed by later circulation of type B. The late season third peak is being attributed to increased healthcare-seeking for respiratory symptoms resulting from concerns about COVID-19 infection.
• In the U.S., influenza-associated hospitalization rates during the 2020-2021 influenza season were the lowest recorded since this data collection began in 2005.
• During the 2019-2020 influenza season, almost 200 children in the U.S. died from illness associated with influenza; more than half of the deaths for which the child’s medical history was known (57%) were in children who did not have an underlying medical condition. Four of five children who died were not vaccinated. During the 2020-2021 influenza season only one pediatric death caused by influenza was reported. The CDC estimates that influenza-related deaths in children are higher than reported based on testing rates and under-recognition among children whose deaths do not occur in a hospital setting. For example, based on such factors, CDC estimates that about 430 children likely died from influenza infection during the 2019-2020 season.
• While rates of adult influenza vaccination increased in the U.S. during the 2020-2021 season (50-55% compared with 48% the previous year), childhood influenza vaccination rates decreased by about 4% (from 62% to 58%). Vaccination of pregnant women and healthcare workers also decreased slightly, and racial and ethnic disparities remained.
• Vaccine effectiveness during the 2019-2020 influenza season were estimated to be about 41% against A(H1N1)pdm09 overall, but only 7% against newer emerging variants. Because of low rates of disease during the 2020-2021 season, vaccine effectiveness could not be determined with certainty.

Factors to consider for the upcoming influenza season

Globally, rates of influenza during the 2020-2021 season were significantly lower than typical. According to the WHO, several hypotheses might explain this observation, with the possibility of a convergence of some factors:

• Lower levels of influenza testing due to supply shortages, health-seeking behaviors, and lab capacity although based on available data, the testing hypothesis does not seem likely to have played any major role in the aberration of expected case numbers.
• The use of contact tracing, isolation and quarantine of individuals diagnosed with or suspected of having COVID-19, coupled with population-level mitigation strategies, may have reduced spread. Examples of population-level interventions included stay-at-home orders, masks and social distancing; widespread closure of workplaces, schools and restaurants; cancellation of mass gatherings; and reduced international travel through flight cancellations and border closings. While these measures generally are not employed during influenza pandemics because of the characteristics of pandemic influenza strains that make these measures less effective, seasonal influenza may have been more susceptible to such measures when coupled with populational immunity (whether from natural or vaccine-induced exposures). Limitations regarding this theory include the fact that adherence to these measures was not universal or, in some places, stringent.
• While co-circulating viruses may benefit from presenting in the same host, others compete. In this manner, it is possible that when the immune system was activated by SARS-CoV-2, the innate immune response was already primed if an influenza or other respiratory virus exposure occurred. Alternatively, the adaptive immune response afforded some level of cross-priming allowing for faster responses to a secondary infection.

Because the reasons for decreased influenza circulation last year have yet to be understood and because of waning immunity among individuals due to fewer opportunities for exposure, the potential for more severe outbreaks and an earlier than normal start to the season exists. Further, only time will tell which strains will most commonly circulate and whether any of them are novel variants.

Influenza vaccines

• Only quadrivalent influenza vaccines will be available in the U.S. for the 2021-2022 season.
• The influenza A strains have been updated, while the influenza B strains remain the same. All vaccines will contain the following three strains:
  • B/Washington/02/2019 (Victoria lineage)-like virus
  • B/Phuket/3073/2013 (Yamagata lineage)-like virus
  • A/Cambodia/e0826360/2020 (H3N2)-like virus (new)
• The H1N1 strain (new) will vary based on vaccine type:
  • Egg-based inactivated and live viral versions will include A/Victoria/2570/2019 (H1N1)pdm09-like virus
  • Non-egg-based versions (cell-culture-based Flucelvax^® and recombinant Flublok^®) will contain A/Wisconsin/588/2019 (H1N1)pdm09-like virus
• As per COVID-19 revised guidelines, influenza and COVID-19 vaccines can be administered without regard to timing (i.e., at the same visit or during any time interval of separation); however, a potential for increased reactogenicity should be considered. Further, if two vaccines given at the same visit might cause a local reaction, the vaccines should be administered in different limbs when possible.
• Changes have been recommended related to the timing of influenza vaccination to account for evidence of waning immunity in some adults. The CDC is still reviewing these recommendations; however, proposed timing is as follows:
  • People should be encouraged to get vaccinated by the end of October whenever possible, but vaccinations can continue beyond that time as long as influenza is still circulating in a community.
  • Children between 6 months and 8 years of age who require two doses should be vaccinated as soon as vaccine becomes available; likewise, children who only require one dose can be vaccinated as soon as vaccine is available as waning immunity appears to be less of a concern in this age group.
  • Pregnant women in the third trimester should be vaccinated as soon as vaccine becomes available given the benefit of maternal antibodies for the baby during the first six months of life before vaccination is possible.
  • For all other adults, vaccination should be avoided in July and August unless there is a concern that later vaccination may not be possible.
• About 87% of the influenza vaccine supply will be thimerosal-free or thimerosal-reduced. About 18% of the supply will be free of egg protein.

Takeaways for clinical practice

While the upcoming influenza season will be more unpredictable than usual, we can prepare ourselves, our patients and our communities by implementing the following practices:

• First and foremost, encourage every patient who can be vaccinated to do so, particularly given the potential for waning immunity and the unknowns related to co-circulation of these viruses in communities that have resumed normal activity.
• Vaccination of most individuals should occur during September and October, as per the proposed changes to guidelines.
• Be astute in considering influenza as a diagnosis in patients with respiratory symptoms even if you do not typically see influenza at that time of year.
• Monitor for unusual or complex presentation of either influenza or COVID-19 since we have yet to develop a firm understanding of how these two pathogens will interact when community activity is more typical, compared with last fall.

Resources

• WHO report
• CDC supply guidance
• FluView surveillance tool