Overview

Influenza (commonly known as the flu) is a common, highly mutable, and contagious respiratory viral infection that can infect the nose, throat, and sometimes the lungs, causing symptoms including fever, chills, muscle aches, cough, congestion, runny nose, headaches, and fatigue.

For most people, influenza resolves on its own and they won’t need medical care, recovering in less than two weeks. However, influenza can cause severe illness and complications, particularly among children under age 2, adults over age 65, people with chronic illnesses or with weakened immune systems, and pregnant women. For example, during the 2019-2020 influenza season in the US that was rated by the CDC as moderate, there were an estimated 35 million influenza-related illnesses, including 380,000 hospitalizations and 20,000 deaths.¹

Influenza is treated primarily with rest and fluids to let the body fight the infection on its own. Over-the-counter anti-inflammatory pain relievers may help with symptoms. An annual influenza shot can help prevent influenza and limit its complications. 

The influenza virus constantly undergoes slight genetic mutations. These mutations can lead to “drifts,” or alterations of the virus’s surface proteins, making it more difficult for the immune system and influenza vaccines to properly respond to the virus or prevent infection.² Abrupt mutations result in antigenic “shifts”, creating novel influenza viruses capable of causing global or pandemic influenza vs. seasonal strains of influenza.

Many influenza vaccines are quadrivalent; therefore, they are designed to protect against the four main groups of influenza Type A and B viruses that research indicates are most likely to spread and cause illness among people during the upcoming influenza season.³ 

In the U.S., seasonal influenza vaccines protect against the influenza A(H1) virus, the influenza A(H3) virus, the influenza B/Yamagata lineage virus, and the influenza B/Victoria lineage virus.⁴

Because influenza is highly mutable, seasonal influenza vaccines are updated each year, but with varying results—with its effectiveness in some years being as low as 10%. For example, the 2018-2019 influenza vaccine ultimately turned out to be a poor match for the viruses circulating that season, at only 29% effecicacy.⁵ 

Each of the four seasonal influenza vaccine virus components are selected based on the following: ⁴ 

• Which influenza viruses are making people sick prior to the upcoming influenza season
  • The extent to which those viruses are spreading prior to the upcoming influenza season 
  • How well the previous season’s influenza vaccine may protect against those influenza viruses
  • The ability of seasonal influenza vaccine to provide cross-protection against a range of related influenza viruses of the same type or subtype/lineage

For decades it has been common knowledge that the influenza vaccine doesn’t match well when the CDC, WHO and other respected public health organizations tell vaccine manufacturers, working many months ahead of influenza season, which influenza strain will circulate later that year. This error is common enough to be termed a “mismatched” influenza vaccine. Recently, more epidemiologists are now pointing toward the mutations of the influenza vaccine strain itself to explain these mutational drifts that may impact seasonal influenza vaccine efficacy.⁶

Prevalence  

Global

• Children younger than 18 are more than twice as likely to develop a symptomatic influenza virus infection than adults 65 and older⁷ 
• Worldwide, annual flu epidemics are estimated to result in about three to five million cases of severe illness, and about 290,000 to 650,000 respiratory deaths⁸ 

United States

• Each season, about eight percent of the U.S. population (roughly 26 million) are infected with influenza, with a range of between 3 percent and 11 percent, depending on the season⁷ 
• Between 2010 and 2020, the CDC estimates that influenza resulted in a total of nine to 41 million related illnesses, 140,000 – 710,000 hospitalizations and 12,000 – 52,000 deaths annually⁹ 
• The total annual US economic burden, including 44 million working days lost because of illness, is $87.1 billion¹⁰
  • 83% of that total annual economic burden is associated with influenza deaths – costing the U.S. nearly $72 billion a year
  • 8% of the total cost is due to outpatient visits ($6.8 billion) 
  • 7% of the total cost is from hospital admissions ($6 billion)

During the 2019–2020 season, the total number of influenza deaths in children reported to CDC was 199. Prior to 2019-2020, the 2017-2018 season had the highest reported number of pediatric deaths, with 188 pediatric deaths reported¹¹

Symptoms  

According to the CDC, influenza symptoms include the following:⁷ 

• Cough 
• Headaches 
• Sore throat 
• Fatigue (tiredness) 
• Runny or stuffy nose
  • Muscle or body aches 
• Fever* or feeling feverish/chills
  • Some people may have vomiting and diarrhea, though this is more common in children than adults. 

*Note: not everyone with influenza will have a fever. 

Contagiousness: 

• People with influenza are most contagious in the first three to four days after their illness begins. 
• Some otherwise healthy adults may be able to infect others beginning one day before symptoms develop and up to five to seven days after becoming sick. 
• Some people, especially young children and people with weakened immune systems, might be able to infect others for an even longer time. 

Causes and Complications 

Influenza primarily spreads through the tiny droplets made when individuals contagious with the virus (people are typically most contagious in the first three to four days after illness begins) cough, sneeze, or talk.¹² These droplets can be inhaled, or less frequently, picked up by touching a surface or object that has influenza virus on it and then touching one’s own mouth, nose—or even eyes.⁷ 

Anyone can get sick with influenza, even healthy people, and serious problems related to influenza can occur to anyone at any age, but some people are at higher risk of developing serious flu-related complications, such as pneumonia. Some of these complications can be life-threatening and result in death.¹³ 

Additional complications include sinus and ear infections, inflammation of the heart (myocarditis), brain (encephalitis) or muscle tissues (myositis, rhabdomyolysis), and multi-organ failure (for example, respiratory and kidney failure).¹³ 
Infection of the respiratory tract can trigger an extreme inflammatory response in the body and can lead to sepsis, the body’s life-threatening response to infection. Influenza can also make chronic medical problems worse: for example, people with asthma may experience asthma attacks while they have the flu, and people with chronic heart disease may experience a worsening of their condition.¹³

Treatments and Prevention 

The CDC recommends that people stay home for at least 24 hours after their fever is gone, except to get medical care or other necessities. The fever should pass without the need to use any fever-reducing medicine.¹⁴ 

The annual influenza vaccine is the first line of defense in protecting the population against influenza viruses. However, existing flu vaccines can only induce immunity against a narrow range of recently circulating strains. These strains tend to change every flu season, providing only partial and temporary, season-by-season protection. New studies are also finding that influenza vaccine effectiveness is significantly lower among immunocompromised adults compared with non-immunocompromised adults.¹⁵

Currently approved treatments, or antivirals (oseltamivir, zanamivir and peramivir), work best when taken within 48 hours of onset of flu symptoms. Even approved antiviral small molecule treatments, while they may shorten duration of fever and symptoms, are not effective in patients who are hospitalized with influenza and may result in virus mutations leading to emergence of antiviral-resistant strains of influenza virus.

SAB’s THERAPEUTIC PROGRAM FOR INFLUENZA 

SAB is developing a first-in-class fully human broadly neutralizing polyclonal antibody treatment aimed to provide long-lasting efficacy for post-exposure prophylaxis and treatment of influenza A and B in patients at high-risk for severe influenza outcomes. 

References/More Information  

¹ https://www.cdc.gov/flu/about/burden/2019-2020/archive-09292021.html#:~:text=The%20overall%20burden%20of%20influenza,hospitalizations%2C%20and%2020%2C000%20flu%20deaths. 

² https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719499/

³ https://www.cdc.gov/flu/about/viruses/types.htm

⁴ https://www.cdc.gov/flu/prevent/vaccine-selection.htm 

⁵ https://www.cdc.gov/flu/vaccines-work/2018-2019.html 

⁶ https://www.science.org/content/article/why-flu-vaccines-so-often-fail 

⁷ https://www.cdc.gov/flu/about/keyfacts.htm 

⁸ https://www.who.int/news-room/fact-sheets/detail/influenza-%28seasonal%29 

⁹ https://www.cdc.gov/flu/about/burden/index.html 

¹⁰ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885332/ 

¹¹ https://www.cdc.gov/flu/spotlights/2020-2021/pediatric-flu-deaths-reach-new-high.htm 

¹² https://www.healthline.com/health/influenza/facts-and-statistics 

¹³ https://www.cdc.gov/flu/symptoms/symptoms.htm 

¹⁴ https://www.cdc.gov/flu/prevent/prevention.htm 

¹⁵ https://pubmed.ncbi.nlm.nih.gov/24491087/