Influenza 2026, Testing & Treatment

As of late January 2026, the U.S. is facing an aggressive respiratory surge. The dominant pathogen is Influenza A, specifically a highly mutated H3N2 variant known as Subclade K. This variant currently accounts for over 90% of U.S. cases. Because Subclade K emerged after the current vaccine was finalized, we are seeing significant antigenic drift and high infection rates, even in vaccinated populations. Currently, Flu positivity is at 18%, while COVID-19 positivity is at 5.3%. When a patient presents with sudden-onset respiratory distress today, the pre-test probability for Influenza A is exceptionally high. Read more about the current outbreak in my last post on this flu season.

The Golden Rule: Empiric Treatment

In the Urgent Care setting, your clinical judgment often outpaces the lab. Per CDC guidance, do not wait for test results to start antivirals in high-risk patients. If they present with suspected flu, start treatment.

Defining the High-Risk Population

Who is officially considered high risk? The CDC’s definition is specific: It includes adults 65 and older, children under 5, especially those under 2, and anyone who is pregnant or up to two weeks postpartum. It also includes those with chronic conditions like Asthma and COPD, heart disease, diabetes, and the immunocompromised. For these patients, the risk of complications like pneumonia is significantly higher.

Navigating the Negative Result

What if that high-risk patient’s rapid antigen test is negative? Don’t be misled. Because of the moderate sensitivity of RIDTs, a negative result does not rule out influenza during peak circulation. If your suspicion is high, especially in a patient with a COPD or Asthma flare, continue empiric treatment regardless of that negative result.

The Low-Risk Outpatient

For your previously healthy, low-risk patients, testing is optional. If flu is widespread in your community, a clinical diagnosis is sufficient. Only test if the result will change your management plan, such as prescribing antivirals within the 48-hour window or protecting high-risk household contacts.

Clinical Suspicion

How do you ‘suspect’ flu before the swab? Clinical signs are your first indicator. Unlike many respiratory viruses that start with a slow ‘creep,’ flu typically hits suddenly. Look for the rapid onset of high fever, intense myalgia, and profound fatigue. A patient who felt fine at breakfast but is bedridden by lunch is your classic flu presentation.

Can you differentiate by symptoms alone? It’s tough, but look for the nuances. Flu is more often associated with that ‘sudden hit’ of body aches. While COVID-19 symptoms often evolve more gradually, it is still more likely to involve prolonged fatigue or a new loss of taste or smell, which is rare with the flu. Common colds are generally milder and dominated by upper airway congestion and runny nose.

Current Context: January 2026 Data

Context matters. As of late January 2026, we are seeing high national flu activity. In contrast, COVID-19 test positivity is currently low. While COVID remains a factor, the high flu-to-COVID ratio means any sudden ‘flu-like illness’ right now has a high pre-test probability of being influenza.

---

Testing

Rapid Antigen Tests (RIDTs)

These target viral nucleoproteins. They’re fast, 10 to 15 minutes, and available as point-of-care or OTC home tests. While specificity is high at 90–95%, sensitivity is only moderate, typically 50–70%. Remember: In high-prevalence settings, a negative antigen test does not rule out infection.

Rapid Molecular (NAATs)

Rapid Molecular NAATs, like the ones using LAMP or NEAR technology, provide results in 15 to 30 minutes with significantly higher sensitivity, around 90–95%, approaching lab-based PCR. They are the preferred POC choice for most outpatients. Many of these provide simultaneous testing for FLU and COVD.

Lab-Based PCR

This is our gold standard. These are laboratory-based, often multiplexed for Flu A, B, and COVID-19. Expect a turnaround of 45 minutes to several hours in-house, or 1–3 days if sent out. Sensitivity and specificity are both 98% or higher.

Performance Comparison Table for Reference

Test Type	Technology	Sensitivity	Specificity	Turnaround Time
Antigen (RIDT)	Immunoassay	50–70%	90–95%	10–15 Minutes
Rapid NAAT	LAMP / NEAR	90–95%	>95%	15–30 Minutes
Lab RT-PCR	Molecular	>98%	>99%	45 Min – 3 Days

---

Treatment

The Big Four

When the diagnosis is confirmed or strongly suspected in high-risk patients, we have four FDA-approved antivirals. For the outpatient setting, your primary tools are Oseltamivir, Baloxavir, and Zanamivir. The fourth, Peramivir, is a single-dose IV infusion typically reserved for those who cannot tolerate oral or inhaled medications.”

Oseltamivir (Tamiflu) vs. Baloxavir (Xofluza)

Oseltamivir is our workhorse. It’s a neuraminidase inhibitor approved for all ages, even infants. It’s the preferred choice for pregnant and breastfeeding individuals. Its main drawbacks? A 5-day course and common GI side effects like nausea and vomiting. Baloxavir is different. It’s a cap-dependent endonuclease inhibitor. It’s a single dose approved for patients 5 and older. While convenient, it is not recommended for pregnant or breastfeeding patients due to a lack of data.

Zanamivir (Relenza) and Peramivir (Rapivab)

Zanamivir is an inhaled powder for those 7 and older. It’s excellent for patients who can’t swallow pills, but it is strictly contraindicated in patients with underlying airway disease like Asthma or COPD due to the risk of bronchospasm. Peramivir, IV only, is approved for patients 6 months and older. Although single dose, the IV formulation limits its use outside the hospital.

Renal Adjustments and Dialysis

Oseltamivir and Peramivir require dosage modifications based on creatinine clearance. For patients on hemodialysis, Oseltamivir is typically dosed after sessions. Interestingly, Baloxavir and Zanamivir do not require renal adjustment, making them a simpler option for patients with chronic kidney disease, though clinical data for those on dialysis is still limited.

Immunocompromised Strategy

For your immunocompromised patients, the CDC recommends Oseltamivir over Baloxavir. These patients often experience prolonged viral shedding, so be prepared for a longer treatment course.

Baloxavir Marboxil (Xofluza) Prescribing Details

• Minimum age: 5 years
• Time window from symptom onset: 48 hrs
• Caution: “Use caution with coadministration of products containing polyvalent cations due to reduced exposure.” That means if you are taking Xofluza, you should avoid the following for a few hours before and after your dose:
  • Dairy Products: Milk, cheese, yogurt, or calcium-fortified orange juice.
  • Antacids: Tums (calcium), Maalox/Mylanta (magnesium/aluminum).
  • Supplements: Multivitamins, Iron pills, or Zinc lozenges.
  • Laxatives: Many contain magnesium.
• Special Populations:
  • Pregnancy: No
  • Breastfeeding: No
  • Renal insufficiency (CrCl < 50 mL/min) / Dialysis: No

Osetlamivir (Tamiflu) Prescribing Details

• Minimum age: 2 Weeks
• Time window from symptom onset: 48 hrs
• Caution: Oral suspension contains sorbitol, use caution in hereditary fructose intolerance.
• Special Populations:
  • Pregnancy: Yes, observational data. Recommended by the CDC up to 2 weeks post partum.
  • Breastfeeding: “Poorly excreted in breast milk; adverse effects unlikely” according to the CDC
  • Renal insufficiency: Adults, treatment: CrCl >60–90 mL/min 75 mg BID x5d; CrCl >30–60 30 mg BID x5d; CrCl >10–30 30 mg daily x5d.
  • ESRD on hemodialysis: 30 mg now, then 30 mg after every HD cycle (treatment duration ≤5 days). ESRD on CAPD: single 30 mg dose now. ESRD without dialysis: not recommended.

Peramivir (Rapivab) Prescribing Details

• Minimum age: 6 months
• Time window from symptom onset: 48 hrs
• Caution Use caution due to risk of serious skin reactions and anaphylaxis.
• Special Populations:
  • Pregnancy: No
  • Breastfeeding: No
  • Renal insufficiency:
    • Adults/adolescents (≥13y), single dose: CrCl ≥50 mL/min 600 mg; CrCl 30–49 200 mg; CrCl 10–29 100 mg.
    • Peds (2–12y): CrCl ≥50 12 mg/kg; CrCl 30–49 4 mg/kg; CrCl 10–29 2 mg/kg (max 600 mg). Peds 6 months to <2 years with CrCl <50: no data to recommend an adjustment.

Zanamivir (Relenza) Prescribing Details

• Minimum age: 7 years
• Time window from symptom onset: 48 hrs
• Caution: Avoid in patients with milk protein allergy. Avoid in asthma or COPD due to bronchospasm risk. Use caution in patients with underlying airway disease.
• Special Populations:
  • Pregnancy: No
  • Breastfeeding: No
  • Renal insufficiency or Dialysis: No dose adjustment

CDC Dosing Chart