Pulmonary · PANCE / PANRE

Influenza

Written & clinically reviewed by Ryan Busch, PA-C · Updated August 2026 · Report an error

Acute viral respiratory illness from influenza A or B with seasonal epidemics and pandemic potential.

Also known as: influenza, flu, seasonal flu, influenza A, influenza B

Overview

Acute respiratory illness caused by influenza A or B viruses (single-stranded segmented RNA, family Orthomyxoviridae), characterized by abrupt onset of fever, myalgia, headache, and respiratory symptoms.

Epidemiology

Annual seasonal epidemics in temperate regions (Northern Hemisphere November-April). Causes 9-41 million illnesses, 100,000-700,000 hospitalizations, and 12,000-52,000 deaths annually in the US. Antigenic drift drives seasonal variation; antigenic shift in influenza A drives pandemics (1918, 1957, 1968, 2009).

Try two board-style Influenza questions

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Question 1PulmonaryEasy
A 26-year-old previously healthy woman has 3 days of dry cough, low-grade fever, myalgias, and mild dyspnea on exertion. Temperature is 100.6°F (38.1°C), HR 96/min, RR 18/min, and SpO2 96% on room air. Lung exam reveals scattered fine crackles without consolidation. A chest radiograph shows bilateral diffuse interstitial infiltrates. Rapid PCR is positive for influenza A, 36 hours after symptom onset. Which of the following is the most appropriate first-line management?
  • AOral oseltamivir
  • BOral rimantadine
  • CInhaled ribavirin
  • DOral valacyclovir
Reveal answer & full explanation
Correct answer: A — Oral oseltamivir
  • AOral oseltamivir✓
  • BOral rimantadine
  • CInhaled ribavirin
  • DOral valacyclovir

Why Oral oseltamivir is correct

  • This is influenza A (confirmed by rapid PCR) with the diffuse interstitial pattern typical of viral pneumonia rather than lobar bacterial consolidation
  • Neuraminidase inhibitors block release of virus from infected cells and shorten illness when started within 48 hours of symptom onset, met here at 36 hours
  • Oral oseltamivir 75 mg twice daily for 5 days is the standard first-line antiviral for uncomplicated influenza in adults

Why the others are wrong

  • Oral rimantadine — an adamantane active only against influenza A, but essentially all circulating strains carry M2 resistance, so it is no longer recommended for treatment
  • Inhaled ribavirin — reserved for severe respiratory syncytial virus infection in immunocompromised patients, not influenza (buzzword-matching "antiviral")
  • Oral valacyclovir — inhibits herpesvirus DNA polymerase and has no activity against influenza virus
Question 2PulmonaryEasy
A 34-year-old woman presents with 24 hours of fever to 39.1°C, myalgias, headache, dry cough, and sore throat during peak influenza season. She has no significant medical history and is not pregnant. Exam shows clear lungs and a temperature of 38.9°C. A rapid molecular influenza test is positive for influenza A. Which of the following is the most appropriate first-line pharmacologic therapy?
  • AOral azithromycin
  • BOral acyclovir
  • COral oseltamivir
  • DOral amantadine
Reveal answer & full explanation
Correct answer: C — Oral oseltamivir
  • AOral azithromycin
  • BOral acyclovir
  • COral oseltamivir✓
  • DOral amantadine

Why Oral oseltamivir is correct

  • This patient has confirmed influenza A within 48 hours of symptom onset, and antiviral therapy is recommended to shorten illness duration and reduce complications
  • Oseltamivir is a neuraminidase inhibitor that blocks release of progeny virions from infected cells
  • It is the first-line oral agent for influenza A and B in adults and children, and is most effective when started within 48 hours of symptom onset

Why the others are wrong

  • D) Oral amantadine — amantadine is an M2 ion channel blocker active only against influenza A, but widespread resistance among circulating strains has rendered it ineffective and it is no longer recommended
  • B) Oral acyclovir — acyclovir treats herpesvirus infections such as herpes simplex virus (HSV) and varicella-zoster virus (VZV) and has no activity against influenza viruses
  • A) Oral azithromycin — azithromycin is a macrolide antibiotic targeting bacterial respiratory pathogens such as atypical pneumonia organisms and provides no antiviral benefit for influenza

Additional high-yield points

  • Adjunctive supportive care with hydration, rest, and antipyretics complements antiviral therapy in uncomplicated cases
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Risk factors

  • Age <2 or ≥65 years
  • Pregnancy (especially 2nd and 3rd trimester) and up to 2 weeks postpartum
  • Chronic comorbidities: pulmonary (asthma, COPD), cardiovascular, renal, hepatic, neurologic, metabolic (diabetes), hematologic
  • Immunosuppression: HIV, cancer, transplant, immunosuppressive medications
  • Morbid obesity (BMI ≥40)
  • Residents of long-term care facilities
  • American Indian/Alaska Native populations (increased severe disease)

Pathophysiology

Influenza virus binds sialic acid receptors on respiratory epithelium via hemagglutinin (HA). Viral neuraminidase (NA) cleaves sialic acid to release new virions. Local respiratory epithelial injury, systemic inflammatory cytokine response, and impaired mucociliary clearance predispose to secondary bacterial pneumonia. Influenza A subtypes (H1N1, H3N2) and influenza B lineages (Victoria, Yamagata) co-circulate.

Clinical presentation

Symptoms

  • Abrupt onset (over hours) of fever, chills, myalgia, headache, fatigue
  • Respiratory: dry cough, sore throat, nasal congestion/rhinorrhea
  • GI symptoms (vomiting, diarrhea) more common in children
  • Severe prostration disproportionate to other URI causes
  • Usually self-limited 3-7 days, but cough and malaise may linger 1-2 weeks

Signs / physical exam

  • Fever, often 38.5-40°C
  • Conjunctival injection, mild pharyngeal erythema without exudate
  • Mild cervical lymphadenopathy
  • Respiratory exam usually unremarkable unless complicated (rales, wheeze suggest pneumonia)

Differential diagnosis

  • Common cold (rhinovirus, coronavirus) — Less systemic illness, prominent rhinorrhea/sore throat without high fever or severe myalgia
  • COVID-19 — Anosmia/ageusia prominent; positive SARS-CoV-2 testing; can have prolonged illness
  • RSV (older adults) — Wheeze, hypoxia; can be severe; multiplex PCR distinguishes
  • Acute bronchitis — Cough-predominant, mild systemic symptoms
  • Streptococcal pharyngitis — Sore throat with tonsillar exudate, anterior cervical adenopathy, no cough; positive strep test
  • Mononucleosis — Pharyngitis with posterior cervical adenopathy, splenomegaly, atypical lymphocytes; positive heterophile
  • Bacterial pneumonia (often post-influenza) — Persistent or recurrent fever after initial flu improvement, focal infiltrate, purulent sputum

Diagnostic workup

Labs

  • Often clinical diagnosis during peak season in otherwise well outpatients
  • Rapid influenza diagnostic tests (RIDT) — point-of-care, modest sensitivity (~50-70%), high specificity
  • Rapid molecular assays (NAAT/PCR) — higher sensitivity, preferred when treatment decision or hospitalization at stake
  • RT-PCR — gold standard; multiplex panels can simultaneously detect SARS-CoV-2, RSV, influenza
  • Severe disease: CBC (often lymphopenia), CMP, lactate, blood cultures if bacterial superinfection suspected

Imaging

  • Chest radiograph if hypoxia, focal findings, or worsening symptoms — to exclude primary viral pneumonia or secondary bacterial pneumonia
  • CT chest if diagnosis uncertain or complicated

Diagnostic algorithm

AntiviralRouteDoseNotes
OseltamivirOral75 mg BID × 5 daysFirst-line; renal dose adjust; nausea common
ZanamivirInhaled10 mg (2 puffs) BID × 5 daysAvoid in asthma/COPD (bronchospasm)
PeramivirIV600 mg single doseFor patients unable to tolerate oral/inhaled
BaloxavirOral40-80 mg single doseEndonuclease inhibitor; single-dose convenience; resistance emerging
FDA-approved antivirals for influenza in adults (IDSA 2018).

Treatment

First-line

  • Antivirals — start ASAP for symptomatic patients (ideally within 48 h of onset):
  • Oseltamivir 75 mg BID × 5 days (oral; renal dose adjust) — most widely used
  • Zanamivir 10 mg (2 inhalations) BID × 5 days — avoid in asthma/COPD (bronchospasm risk)
  • Peramivir 600 mg IV × 1 dose — for those unable to tolerate PO
  • Baloxavir marboxil 40-80 mg PO × 1 dose — endonuclease inhibitor; single-dose; emerging resistance
  • Hospitalized patients: treat regardless of symptom duration
  • Outpatients: treat if high-risk (age, pregnancy, chronic conditions, immunocompromise, severe illness) or within 48 h of onset in healthy patients
  • Supportive care: hydration, rest, acetaminophen/NSAIDs for fever and myalgia (avoid aspirin in children — Reye syndrome)

Second-line / adjunct

  • Treat secondary bacterial pneumonia (S. pneumoniae, S. aureus including MRSA, H. influenzae): empiric beta-lactam ± vancomycin/linezolid based on severity
  • Post-exposure chemoprophylaxis with oseltamivir or zanamivir for high-risk unvaccinated close contacts (within 48 h of exposure) — 7 days
  • Prevention is paramount: ANNUAL influenza vaccination for everyone ≥6 months
  • Vaccine options: standard inactivated (IIV3/IIV4), high-dose (adults ≥65), adjuvanted (adults ≥65), recombinant (RIV4), live-attenuated nasal (LAIV4, ages 2-49 non-pregnant non-immunocompromised)
  • Infection control: droplet precautions in hospitals; isolation of infected patients

Complications

  • Primary influenza viral pneumonia (especially in pregnancy, immunocompromised)
  • Secondary bacterial pneumonia (S. pneumoniae, S. aureus including MRSA, H. influenzae) — often biphasic with initial improvement then deterioration
  • ARDS, multi-organ failure
  • Exacerbation of chronic conditions: COPD, asthma, heart failure
  • Myocarditis, pericarditis
  • Encephalitis, transverse myelitis, Guillain-Barré syndrome
  • Myositis, rhabdomyolysis (especially influenza B in children)
  • Reye syndrome (children given aspirin)

PANCE pearls

  • Abrupt-onset fever, myalgia, and dry cough in a previously well adult during flu season is influenza until proven otherwise.
  • Antiviral benefit is greatest within 48 h of symptom onset — do not delay for testing in high-risk patients.
  • Biphasic illness (initial improvement, then recurrent fever and worsening) suggests secondary bacterial pneumonia, often S. aureus or S. pneumoniae.
  • AVOID aspirin in children with influenza or varicella — Reye syndrome risk.
  • Annual vaccination is the most important preventive intervention; everyone ≥6 months should receive it absent specific contraindication.

References

  • IDSA 2018 — Clinical Practice Guidelines by IDSA: 2018 Update on Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management of Seasonal Influenza (Uyeki et al., Clin Infect Dis 2019)
  • CDC 2024 — Prevention and Control of Seasonal Influenza with Vaccines: ACIP Recommendations 2024-25 (MMWR Recomm Rep)
  • Baloxavir Trials — Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents (Hayden et al., NEJM 2018)
  • Cochrane Oseltamivir — Neuraminidase Inhibitors for Preventing and Treating Influenza in Healthy Adults and Children (Jefferson et al., Cochrane Database Syst Rev 2014)

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Commonly confused with

vs Community-Acquired Pneumonia

Related Pulmonary diagnoses

AsthmaChronic Obstructive Pulmonary Disease (COPD)Community-Acquired Pneumonia (CAP)Hospital-Acquired and Ventilator-Associated Pneumonia (HAP/VAP)Aspiration Pneumonia and PneumonitisTuberculosis (Active and Latent)Pulmonary Embolism (PE)Pulmonary HypertensionPneumothorax (Spontaneous and Tension)Pleural EffusionAcute Respiratory Distress Syndrome (ARDS)Lung Cancer (Small Cell and Non-Small Cell)BronchiectasisCystic Fibrosis

Differentials & related conditions

COVID-19Bronchiolitis (RSV)Acute BronchitisGroup A Streptococcal PharyngitisInfectious Mononucleosis (EBV)

Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.