Influenza is a highly contagious viral infection that typically occurs during the winter months. It is caused by influenza A, B, and C viruses. There are various subtypes of influenza A viruses, which are classified based on their hemagglutinin (H) and neuraminidase (N) surface antigens. Influenza viruses frequently mutate, resulting in the emergence of new subtypes and strains. Symptomatic patients may present with sudden onset of high fever, headache, myalgias, arthralgias, nonproductive cough, and malaise. Inflammatory markers are usually normal or slightly elevated. The diagnosis can often be established based on clinical presentation, but PCR testing may be used to confirm the diagnosis. Usually, symptoms are self-limited and supportive treatment is sufficient. However, antiviral therapy may be considered for patients with early or severe disease, especially in those at high risk for complications. Antiviral therapy may reduce the severity and shorten the duration of symptoms, and reduce the risk of developing complications. Rarely, patients may develop secondary bacterial pneumonia, most commonly caused by Staphylococcus aureus or Streptococcus pneumoniae. Hand hygiene, respiratory hygiene, and vaccination can help prevent the spread of influenza.
- Distribution: worldwide
- Seasonal pattern: Most infections occur during the fall and winter (influenza season).
Epidemiological data refers to the US, unless otherwise specified.
- Pathogen: Influenza virus A and B (and rarely influenza C)
- Person-to-person transmission: directly via respiratory droplets (sneezing or coughing) or indirectly through contact with contaminated surfaces
- Influenza A (e.g., H1N1)
- Influenza B/C (less common)
Replication cycle 
- Influenza viruses bind to the respiratory tract epithelium.
- Viral hemagglutinin (H) binds sialic acid residues (neuraminic acid derivatives) on the host cell membrane → virus fusion with the membrane → entry into the cell
- The virus replicates in the nucleus of the cell.
- The new virus particles travel to the cell membrane → formation of a membrane bud around the virus particles (budding)
- Viral neuraminidase (N) cleaves the neuraminic acid → virions exit the cell
- Host cell dies → cellular breakdown triggers a strong immune response
Genetic mutations 
- Two subtypes of viruses (e.g., human and swine influenza) infect the same cell and exchange genetic segments (reassortment) to create new subtypes (e.g., H3N1 → H2N1).
- Occurs in particular when human pathogenic and animal pathogenic influenza viruses exchange genetic information
- Causes pandemics (limited to a specific time period)
- Antigenic drift
Small shifts in a panda's habitat can cause epic dread: Shifts can cause pandemics and drifts cause epidemics.
The clinical presentation of influenza infection is asymptomatic or mild in 75% of cases. Influenza presents with very characteristic features, hence the term “flu-like symptoms”.
- Incubation period: a few hours to several days
- Sudden onset of high fever, chills, headache, arthralgia, myalgia, fatigue, and malaise
- Patients often develop acute bronchitis with a cough that is usually dry but may produce small amounts of clear or blood-tinged sputum.
- Hypotension and bradycardia are common (especially among women and older patients)
General principles 
- During periods of high influenza activity, a clinical diagnosis can often be made based on the presence of typical .
- In general, testing should only be carried out in outpatients if the results will influence management.
- Testing should not delay treatment.
Influenza can present in atypical ways and can also trigger exacerbations in patients with chronic cardiopulmonary diseases. 
Indications for testing 
|Indications for influenza testing |
|High influenza activity||Low influenza activity|
|Outpatients|| || |
|Inpatients|| || |
Laboratory studies 
Molecular assays are the preferred method for detecting influenza virus infection. ; 
- RT-PCR: preferred test for inpatients
- Rapid molecular assay: preferred test for outpatients
Rapid antigen test: can detect various influenza A/B antigens, usually via nasal or pharyngeal swabs
- High specificity but limited sensitivity
- Only indicated if more sensitive tests are unavailable
- Molecular assays are the preferred method for detecting influenza virus infection. ; 
- Additional studies
Further evaluation 
- Evaluate for coinfection (e.g., bacterial superinfection, and/or complications) if any of the following are present:
- Presentation with severe illness
- Clinical deterioration after initial improvement
- Consider evaluation if there is no improvement within 3–5 days of symptom onset.
- Evaluation should be guided by symptoms and may include:
- See “ ” for further details.
- Most acute upper respiratory tract infections are:
- For information on the differential diagnoses of COVID-19, see “Differential diagnoses” in “ .”
|Overview of acute upper respiratory tract infections|
|Most common pathogens||Distinct clinical features||Distinct physical examination findings||Treatment|
|Common cold || || || |
|Influenza || || || |
|COVID-19 || |
|Sinusitis || |
|Laryngitis || |
|Epiglottitis || |
|Croup || |
The differential diagnoses listed here are not exhaustive.
Supportive treatment 
- and 
- to relieve dry cough
Most cases of influenza are self-limited and do not require specific treatment. If antiviral treatment is indicated, treatment should be initiated as soon as possible.
The following recommendations are in line with the 2018 update of the IDSA guidelines on seasonal influenza. The quality of some of the underlying evidence for the use of neuraminidase inhibitors is part of an ongoing and controversial debate. 
All patients with suspected or documented influenza and ≥ 1 of the following:
- Severe or progressive illness
- Hospitalization required
- Consider treating patients with suspected or confirmed influenza and ≥ 1 of the following:
- Onset ≤ 48 hours prior to presentation
- Close contact with high-risk patients
Do not delay the initiation of antiviral therapy while awaiting the results of testing.
- Mechanism of action: inhibits the release of viruses from the host cell
- Greatest benefit if started within the first 48 hours of symptom onset 
- Commonly used agents
Cap-dependent endonuclease inhibitor
- Oral baloxavir marboxil (acute, uncomplicated influenza) 
Consider a longer duration of antiviral treatment in patients with immunosuppression and those who require hospitalization.
Do not use amantadine to treat influenza because of the risk of antimicrobial resistance. 
Patients at high risk for complications of influenza 
- Adults ≥ 65 years of age
- Children < 5 years of age, especially those < 2 years of age
- Patients who are pregnant and in the first 2 weeks postpartum
- Patients with chronic medical conditions (e.g., asthma; , heart disease, CKD, diabetes mellitus; , immunosuppression)
- Those with a BMI ≥ 40 kg/m2
- Nursing home residents
- American Indian, Alaska Native, Black, and Hispanic individuals 
Primary influenza pneumonia
- Epidemiology: less common than secondary bacterial bronchitis or pneumonia
- Clinical features
- Antiviral therapy
- is often necessary. 
- See “ ” for further details.
Secondary bacterial bronchitis and pneumonia
- Etiology: Common causative pathogens include S. pneumoniae, S. aureus (including MRSA), S. pyogenes, and H. influenzae. 
- Clinical features
- Should include coverage for MRSA
Other complications 
- Upper respiratory tract infections
- Exacerbation of chronic diseases: e.g., COPD, asthma, underlying ischemic heart disease, congestive heart failure
- Acute kidney injury
- Rare complications: include cardiac (e.g., pericarditis, myocarditis), musculoskeletal (e.g., myositis, rhabdomyolysis), and neurological complications (e.g., encephalopathy, encephalomyelitis, transverse myelitis, aseptic meningitis, Guillain-Barré syndrome)
We list the most important complications. The selection is not exhaustive.
- Increased in patients at high risk for influenza-related complications (see “Complications” above)
- Average number of annual influenza-related deaths in the US: 23,000 to 48,000
Influenza vaccine 
- General principles of influenza vaccines
- Annual vaccination of all individuals aged ≥ 6 months who do not have a history of anaphylaxis to influenza vaccines
- High-risk groups should be prioritized if there is a limited supply of vaccines.
- See " ” for further details.
- Timing: as soon as the vaccine becomes available
- Vaccine types: Currently available vaccines are quadrivalent.
- Standard precautions
- Isolate or cohort patients.
- See “Droplet precautions” for further details.
- Preexposure prophylaxis: not routinely recommended
- Postexposure prophylaxis: not routinely recommended
- Definition: a type of influenza that originates from animal strains
|Most common types of zoonotic influenza|
|Avian flu ||Swine flu |
|Etiology|| || |
|Clinical features|| |
Special patient groups
Influenza during pregnancy
- Maternal effects
- Fetal effects: associated with an increased risk of birth defects (e.g., congenital heart defects, cleft lip, neural tube defects), fetal death, lower mean birth weight, and small size for gestational age