What is the recommended treatment for a patient with influenza A and COVID‑19 infection?

Treatment of Influenza A and COVID-19 Co-infection

For patients co-infected with influenza A and COVID-19, treat both infections simultaneously: administer oseltamivir for influenza within 48 hours of symptom onset, and for COVID-19, use corticosteroids if the patient requires supplemental oxygen, non-invasive ventilation, or mechanical ventilation. 1, 2

Antiviral Treatment for Influenza A

• Start oseltamivir immediately (within 48 hours of symptom onset) for all co-infected patients, regardless of COVID-19 severity. 1, 3, 2
• Baloxavir is an alternative for patients at high risk of progression from non-severe to severe illness. 2, 4
• Early antiviral initiation is crucial for favorable outcomes and viral suppression in influenza infection. 3
• Treatment-emergent resistant variants may occur with neuraminidase inhibitors and baloxavir, but this has no major impact on recovery. 3

COVID-19 Specific Treatment

Corticosteroids (Critical Decision Point)

• Strongly recommended for patients requiring supplemental oxygen, non-invasive ventilation, or invasive mechanical ventilation. 5, 1
• Strongly recommended AGAINST for hospitalized patients NOT requiring supplemental oxygen. 5, 1
• This represents a stark contrast to influenza, where corticosteroids are strongly recommended against in severe disease. 1

IL-6 Receptor Antagonist (Tocilizumab)

• Consider tocilizumab for COVID-19 patients requiring oxygen or ventilatory support. 5, 1
• This is a conditional recommendation based on low-quality evidence. 5

Remdesivir

• No clear recommendation for patients not requiring invasive mechanical ventilation. 5, 1
• Conditionally recommended AGAINST for patients requiring invasive mechanical ventilation. 5, 1

Antibacterial Therapy Considerations

When to Start Antibiotics

• Do NOT routinely prescribe antibiotics for confirmed COVID-19 pneumonia without evidence of bacterial co-infection. 1
• Start empirical antibiotics when any of the following are present: 1
  • Clinical suspicion of bacterial co-infection
  • Severe pneumonia requiring ICU admission
  • Known colonization with multidrug-resistant organisms

Recommended Antibiotic Regimens (if bacterial co-infection suspected)

For general medical floor patients: 1

• β-lactam (ampicillin-sulbactam, ceftriaxone, or cefotaxime) + macrolide (azithromycin or clarithromycin) or doxycycline
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin or moxifloxacin)

For ICU patients: 1

• β-lactam + macrolide
• Alternative: β-lactam + fluoroquinolone

Antibiotic Stewardship

• Use procalcitonin to guide withholding or early discontinuation of antibiotics. 1
• Discontinue or de-escalate broad-spectrum antibiotics within 48 hours if cultures are negative and the patient is improving. 1
• Strong recommendation against azithromycin in hospitalized COVID-19 patients without bacterial infection. 5, 1

Therapies Strongly Recommended AGAINST

The following should NOT be used in co-infected patients: 5, 1

• Hydroxychloroquine (strong recommendation against, any setting)
• Lopinavir-ritonavir (strong recommendation against)
• Hydroxychloroquine + azithromycin combination (conditional recommendation against)
• Colchicine (conditional recommendation against)
• Interferon-β (conditional recommendation against)

Supportive Respiratory Care

• High-flow nasal cannula or non-invasive CPAP (helmet or facemask) for hypoxemic acute respiratory failure without immediate need for invasive ventilation. 5, 1
• Early prone positioning for severe ARDS (PaO₂/FiO₂ ≤ 100 mm Hg). 1
• Lung-protective ventilation: Tidal volume ≤ 6 mL/kg predicted body weight; plateau pressure ≤ 30 cm H₂O. 1

Anticoagulation

• Strongly recommended to provide anticoagulation to all hospitalized COVID-19 patients. 5, 1

Clinical Context and Risk Factors

• Co-infected patients show symptoms similar to mono-infected patients (fever, cough, dyspnea), but 15.7% have poor outcomes (death/deterioration). 6
• Having comorbidities and being unvaccinated for influenza are important risk factors for poor outcomes. 6
• Most common complications include pneumonia, linear atelectasis, and acute respiratory distress syndrome. 6
• Co-infection is relatively rare (0.54% in one series), but may be underdiagnosed without routine screening. 7

Critical Pitfalls to Avoid

• Do NOT withhold oseltamivir while treating COVID-19—both infections require simultaneous treatment. 3, 2
• Do NOT use corticosteroids in COVID-19 patients who are not hypoxemic, even if they have severe influenza. 5, 1
• Do NOT prescribe antibiotics routinely for confirmed COVID-19 pneumonia without bacterial co-infection. 1
• Do NOT continue broad-spectrum antibiotics beyond 48 hours when cultures are negative and the patient is improving. 1
• Screen for influenza in high-risk COVID-19 patients to identify co-infection, as bacterial co-infection rates in COVID-19 are low but influenza co-infection can worsen outcomes. 6, 7