What are the latest guidelines for managing systemic viral infections?

Management of Systemic Viral Infections

For hospitalized adults with systemic viral infections, management is primarily supportive care with specific antiviral therapy reserved for influenza and COVID-19, while corticosteroids should only be used in severe COVID-19 requiring oxygen or mechanical ventilation. 1, 2

Diagnostic Approach

Rapid viral identification is essential for appropriate management:

• Perform rapid antigen detection assays for influenza virus for epidemiologic purposes and treatment decisions 1
• Tests distinguishing between influenza A and B are preferred 1
• Molecular diagnostic techniques have improved detection of viral pathogens in critically ill patients, with respiratory viral infections detected in 17-53% of patients with severe respiratory illness 3
• SARS-CoV-2 PCR testing should be available for all patients at increased risk, with extended quarantine (≥20 days) recommended for immunocompromised patients due to prolonged viral shedding 1

Antiviral Therapy

Influenza

Early treatment within 48 hours of symptom onset is critical:

• Oseltamivir, zanamivir, amantadine, or rimantadine are effective for influenza A; oseltamivir and zanamivir for influenza B 1
• Early oseltamivir use is associated with reduced mortality in critically ill influenza patients 3
• These drugs are not recommended for uncomplicated influenza with symptoms >48 hours, but may be used to reduce viral shedding in hospitalized patients or for influenza pneumonia 1
• Empiric treatment of suspected bacterial superinfection should cover S. pneumoniae, S. aureus, and H. influenzae with amoxicillin-clavulanate, cefpodoxime, cefprozil, cefuroxime, or a respiratory fluoroquinolone 1

COVID-19

Remdesivir (VEKLURY) is FDA-approved for specific COVID-19 populations:

• Indicated for hospitalized patients and non-hospitalized patients with mild-to-moderate COVID-19 at high risk for progression 4
• Dosing: 200 mg IV loading dose on Day 1, followed by 100 mg IV daily (adults and pediatric patients ≥40 kg) 4
• Treatment duration: 5 days for hospitalized patients not requiring mechanical ventilation/ECMO; 10 days for those requiring invasive mechanical ventilation/ECMO 4
• The European Respiratory Society suggests NOT offering remdesivir to patients requiring invasive mechanical ventilation (conditional recommendation, moderate quality evidence) 1
• Perform hepatic laboratory testing and monitor prothrombin time before and during treatment 4

Other Viral Infections

No established antiviral therapy exists for most other viral infections:

• No antiviral agent with established efficacy for parainfluenza virus, RSV, adenovirus, metapneumovirus, SARS, or Hantavirus 1
• VZV or HSV pneumonia should be treated with parenteral acyclovir 1

Corticosteroid Use

COVID-19 (Strong Evidence)

Corticosteroids demonstrate mortality benefit in severe COVID-19:

• Strongly recommend corticosteroids for patients requiring oxygen, noninvasive ventilation, or invasive mechanical ventilation (strong recommendation, moderate quality evidence) 1
• Dexamethasone 6 mg daily for up to 10 days reduces mortality in patients requiring oxygen or mechanical ventilation 2, 5
• The UK RECOVERY trial showed mortality reduction from 41.4% to 29.3% in patients on invasive mechanical ventilation 1
• Alternative dosing: methylprednisolone 0.5 mg/kg every 12 hours for 5-7 days, particularly with CRP >150 mg/L 2
• Strongly recommend AGAINST corticosteroids for hospitalized COVID-19 patients not requiring supplementary oxygen (strong recommendation, moderate quality evidence) 1

Other Viral Infections (Caution Required)

Corticosteroids are generally contraindicated in non-COVID viral infections:

• Do NOT use corticosteroids routinely in viral pleurisy as they may exacerbate infection and increase mortality 5
• Influenza pneumonia patients should NOT receive corticosteroids due to increased mortality risk 2, 5
• Meta-analyses show increased mortality with corticosteroid use in influenza patients 5
• Risks include increased viral replication, delayed viral clearance, and secondary bacterial infections 5

Therapies NOT Recommended

Multiple agents have been studied but lack efficacy or show harm:

• Strongly recommend AGAINST hydroxychloroquine for COVID-19 (strong recommendation, moderate quality evidence) 1
• Suggest NOT offering azithromycin without bacterial infection (conditional recommendation, very low quality evidence) 1
• Suggest NOT offering hydroxychloroquine and azithromycin in combination (conditional recommendation, moderate quality evidence) 1
• Strongly recommend AGAINST lopinavir-ritonavir (strong recommendation, low quality evidence) 1
• Suggest NOT offering interferon-β (conditional recommendation, very low quality evidence) 1
• Suggest NOT offering colchicine for hospitalized patients (conditional recommendation, very low quality evidence) 1

Immunomodulatory Therapy

IL-6 receptor antagonists have conditional support in severe COVID-19:

• Suggest offering IL-6 receptor antagonist monoclonal antibody therapy (tocilizumab) to hospitalized patients requiring oxygen or ventilatory support (conditional recommendation, low quality evidence) 1
• Suggest NOT offering to patients not requiring supplementary oxygen (conditional recommendation, low quality evidence) 1

Anticoagulation

Thrombotic complications are common in severe viral infections:

• Strongly recommend offering anticoagulation to hospitalized COVID-19 patients (strong recommendation, very low quality evidence) 1
• Cardiovascular complications including thrombotic events are frequent in severe viral infections 6

Supportive Care

Evidence-based supportive care remains the mainstay of management:

• High-flow nasal cannula oxygen therapy (HFNC) or noninvasive CPAP (helmet or facemask) is suggested for hypoxemic acute respiratory failure without immediate indication for invasive mechanical ventilation (conditional recommendation, very low quality evidence) 1
• Non-invasive ventilation in severe respiratory viral infection with acute hypoxemic respiratory failure is associated with high likelihood of transition to invasive ventilation 3
• Lung-protective ventilation with low tidal volumes and plateau pressure is recommended for patients requiring invasive mechanical ventilation 6
• Close monitoring of vital signs including heart rate, respiratory rate, and oxygen saturation 5
• Symptomatic treatment with antipyretics (ibuprofen) when temperature exceeds 38.5°C 5

Critical Pitfalls to Avoid

• Never delay influenza treatment beyond 48 hours of symptom onset 1
• Never use corticosteroids in influenza pneumonia—this increases mortality 2, 5
• Do not use corticosteroids in mild COVID-19 not requiring oxygen 1
• Avoid remdesivir in patients already on invasive mechanical ventilation based on current evidence 1
• Do not routinely use hydroxychloroquine, lopinavir-ritonavir, or azithromycin for COVID-19 1