What are the indications for antiviral therapy in patients with severe viral infections?

Indications for Antiviral Therapy in Severe Viral Infections

Antiviral therapy should be initiated as early as possible in patients with severe sepsis or septic shock of viral origin to reduce morbidity and mortality. 1

General Indications for Antiviral Therapy

• Antiviral therapy is indicated for early treatment of suspected or confirmed influenza among persons with severe, complicated, or progressive illness or who require hospitalization 1
• Antiviral treatment is recommended for persons at higher risk for influenza complications 1
• For COVID-19 patients with severe disease, antiviral therapy should be considered despite limited evidence from randomized controlled trials 1
• Severe primary or generalized varicella-zoster virus infections and disseminated herpes simplex infections require early antiviral treatment with agents such as acyclovir 1
• Cytomegalovirus (CMV) viremia in critically ill patients is associated with poor prognosis and may require treatment in certain populations 1

Specific Viral Pathogens and Recommended Antivirals

Influenza

• Neuraminidase inhibitors (oseltamivir or zanamivir) are recommended for influenza A and B virus infections 1, 2
• Treatment should be initiated within 48 hours of symptom onset for optimal efficacy 2
• For severe influenza infections, early antiviral treatment may reduce the likelihood of lower respiratory tract complications 1
• M2 inhibitors (amantadine and rimantadine) are only active against influenza A virus and have higher rates of toxicity 1

COVID-19

• Alpha-interferon atomization inhalation (5 million U per time for adults, twice daily) can be considered for COVID-19 treatment 1
• Lopinavir/ritonavir (2 capsules twice daily) may be considered for COVID-19 treatment, though evidence is limited 1
• Remdesivir should be considered for hospitalized patients with COVID-19, particularly those with low-flow oxygen requirements and less than 10 days of symptoms 1, 3
• For non-hospitalized high-risk COVID-19 patients, antiviral medications like remdesivir can reduce progression to severe disease when given within 5 days of symptom onset 4

Herpesviruses

• Acyclovir is indicated for severe primary or generalized varicella-zoster virus infections and disseminated herpes simplex infections 1
• For patients with hematologic malignancies, treatment with acyclovir for herpes simplex virus infection has been associated with more favorable febrile response 1
• Valacyclovir and famciclovir are better absorbed after oral administration than acyclovir and have longer dosing intervals 1
• Ganciclovir or foscarnet are indicated for cytomegalovirus infections, particularly in bone marrow transplant recipients 1

Special Populations

Immunocompromised Patients

• Patients with hematologic malignancies or hematopoietic stem cell transplantation require special consideration for antiviral therapy 1, 5
• For neutropenic patients with viral skin or mucous membrane lesions, antiviral treatment is indicated even if these lesions are not the cause of fever 1
• In immunocompromised hosts, the duration of antiviral therapy depends on clinical and radiological resolution, and the degree and duration of immunosuppression 6
• For patients with COVID-19 and hematological malignancies, antiviral treatments may have greater impact due to potentially prolonged viral phase 1

Patients with Sepsis

• Antiviral therapy should be initiated as early as possible in patients with severe sepsis or septic shock of viral origin 1
• Susceptibility to antivirals is highly variable in rapidly evolving viruses such as influenza, requiring updated information during epidemics 1
• The presence of CMV in the bloodstream has been repeatedly found to be a poor prognostic indicator in critically ill patients 1

Timing and Duration of Therapy

• Early initiation of antiviral therapy is crucial for maximum effectiveness 1
• For most viral infections, treatment should be started within the first 48-72 hours of symptom onset 2
• Duration of therapy typically ranges from 7-10 days for most serious infections 1
• Longer courses may be appropriate in patients with slow clinical response, undrainable foci of infection, or immunologic deficiencies including neutropenia 1

Common Pitfalls and Caveats

• Antimicrobial agents, including antivirals, should not be used in patients with severe inflammatory states determined to be of noninfectious cause 1
• Antiviral susceptibility patterns change over time, particularly for influenza viruses, requiring updated information during epidemics 1
• Many antivirals have significant drug interactions that must be considered, particularly in patients on multiple medications 4
• Delayed initiation of antiviral therapy beyond the recommended window (e.g., >48 hours for influenza, >5 days for COVID-19) significantly reduces effectiveness 4
• Underuse of antiviral medications is common, with studies showing that less than 35% of eligible high-risk patients receive recommended antiviral therapy 4

Monitoring During Antiviral Therapy

• Patients should be monitored for vital signs, organ function, and adverse effects of antiviral medications 1, 3
• Regular assessment of liver enzymes, bilirubin, renal function, and complete blood counts is recommended during antiviral therapy 1, 3
• For remdesivir, monitoring for hypersensitivity reactions including infusion-related reactions and transaminase elevations is important 3
• Daily assessment for potential de-escalation of antimicrobial therapy, including antivirals, is recommended in patients with sepsis and septic shock 1