Fall is nearly here, the kids are back in school, and influenza (flu) shots are on the horizon. September and October are the optimal months for influenza vaccination to build immunity before the virus starts circulating in earnest, but it is never too late to get vaccinated. Antibodies do wane, so the CDC recommends vaccination prior to flu season—especially for those at elevated risk of complications.

When does influenza circulate?

When the COVID-19 pandemic emerged, the “typical” flu season changed. Few cases were reported in the 2020-21 flu season due to social distancing, but as society reopened last year there were two distinct waves of infection in the winter and late spring.

Why is influenza a concern?

Before SARS-CoV-2, influenza caused 9 million to 41 million illnesses, 140,000-710,000 hospitalizations, and between 12,000-52,000 deaths per year. People 65 years or older, babies younger than 2 years, and people with certain health conditions are at highest risk of complications to influenza.

Did the flu vaccine help last year?

Preliminary estimates suggest that the risk of complications due to influenza A H3N2 was reduced by vaccination last year even though the vaccine was not a perfect match. Overall vaccine effectiveness was about 34%, meaning those who got a flu shot cut their risk of needing medical care by about 34%.

Did COVID-19 change flu patterns?

It is possible that social distancing modified how the virus circulated. In fact, the CDC considers last year to be among the mildest flu seasons of the last decade. The peak positivity reported by CDC labs was the lowest in at least 25 years of testing despite a higher volume of samples being tested than at any time in the last five years. Although this was a comparatively mild flu season, the CDC estimates that between 8 and 13 million illnesses resulted in 3.7 to 6.1 million hospitalizations and 5,000-14,000 deaths.

Estimate US Influenza Burden
Source: CDC, Estimated U.S. Flu Burden, By Season

Who is at risk for serious flu complications?

Of those who were hospitalized for the flu last year, 93% of adults and 65% of children had an underlying health condition which increased their risk for complications.

Those who are at risk include adults age 65 years or older, children younger than 2, those with asthma, neurological conditions, blood disorders such as sickle cell disease, chronic lung disease (COPD and cystic fibrosis), diabetes, heart or kidney disease, liver disorders, obesity (BMI of 40 or higher), and people with a weakened immune system or young people taking long-term aspirin or salicylate-containing medications. People who live in a long term care facility or a nursing home as well as pregnant women are advised to get a flu shot.

What is contained in this year’s vaccine?

Each year the World Health Organization provides a recommendation for flu vaccine components based on what strains are circulating. This year the vaccine contains updated influenza A (H3N2) and B (Victoria lineage) strains.

Will there be enough vaccine?

Manufacturers have steadily increased production each year in response to demand. This year the expectation is 174-184 million doses will be made available.

Vaccine options

The flu vaccine is available via injection for all ages and a live attenuated influenza vaccine (LAIV) nasal spray (“FluMist”) for ages 2 through 49 years. Both versions come in a quadrivalent (four strain) formulation. The quadrivalent formula contains A(H1N1), A(H3N2), and two influenza B virus strains.

Older adults aged 65 years or more should receive a more potent formulation, referred to as “high-dose,” “quadrivalent,” or “adjuvanted.” The term “adjuvanted” means that the vaccine contains a special component that attracts the attention of the innate immune system to provoke an adequate immune response. The high dose formulation is necessary because as we age the immune system responds less vigorously—this is called immune senescence.

How are the vaccines made?

The vaccines are now available in egg-based, cell-based and recombinant versions.

Egg-based vaccines have been produced for more than 70 years and are the most common flu vaccines available. Both the inactivated (injectable) and live attenuated (nasal spray) vaccines are made with egg-based manufacturing.

Cell-based manufacturing is used to create entirely egg-free vaccines.

The recombinant flu vaccines are made synthetically by inserting the genes for the flu virus antigen into a baculovirus. The baculovirus is then used to infect an FDA-approved host cell line to grow out the antigen in bulk. The antigen is then collected, purified and packaged. The recombinant technology is a known platform used in other vaccines and is the fastest option available.

Can the flu shot make me sick?

The live, attenuated nasal spray contains a weakened version of the influenza virus that only replicates in the cooler air of the nose, not in the warmer areas of the body like the lungs. Neither the injection nor the nasal spray cause you to become sick with influenza, but you may experience some side effects as your body develops immunity.

Does the nasal spray work?

Yes, it works, but the nasal spray vaccine has gone through reformulation since its initial launch and new data needs to be collected to gauge how well FluMist works against certain strains of influenza. This is why the nasal spray is only recommended for those at least risk of flu complications (those ages 2 through 49).

The backstory is this: during the 2009 H1N1 pandemic, data suggested that the nasal spray was not as effective against the A(H1N1) strain but did work as well as the injection against influenza B strains. In 2016-2018, the CDC recommended against using the nasal spray to ensure adequate protection for everyone. Although the manufacturer has introduced a new formulation to combat A(H1N1), not enough people have gotten the nasal spray in recent years for CDC to measure the vaccine’s effectiveness. For this reason, those considered at high risk or age 65 and older are advised to get the inactivated version (injection), not FluMist.

Are flu vaccines safe?

Flu vaccines are safe and reduce the risk of complications due to influenza. The CDC reports that hundreds of millions of influenza vaccine doses have been administered over the past 50 years, and extensive safety studies have been conducted. Some studies have suggested a possible link with Guillain Barré syndrome (GBS), while others have found no link. An elevated risk did appear to be associated with 1976 the swine flu vaccine (approximately 1 in 100,000), but the incidence of GBS since then is estimated to be 1 or 2 per million people vaccinated.


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