What are the latest guidelines for managing systemic viral infections that may cause fever?

Management of Systemic Viral Infections Causing Fever

Core Principle: Targeted Antiviral Therapy Only with Evidence of Viral Disease

Antiviral drugs are indicated only when there is clinical or laboratory evidence of viral disease—empirical antiviral therapy in febrile patients without documented viral infection is not recommended. 1

Diagnostic Approach by Clinical Setting

Critical Care/ICU Patients with New Fever

For critically ill patients with new fever, test for SARS-CoV-2 by PCR based on community transmission levels, and consider multiplex respiratory viral panels for suspected respiratory infections. 1

• Respiratory viral testing: Use commercial multiplex NAAT panels for respiratory specimens when respiratory symptoms are present 1
• Blood testing for systemic viruses: Routine blood testing for herpesviruses (HSV, VZV, EBV, CMV) or adenovirus in immunocompetent ICU patients is not indicated, as fever is rarely related to systemic herpesvirus infection in this population 1
• SARS-CoV-2: Testing should be performed on nasopharyngeal swab, mid-turbinate swab, anterior nasal swab, or saliva; if negative and lower respiratory tract infection suspected, test lower respiratory secretions 1

Immunocompromised/Neutropenic Patients

In febrile neutropenic patients, antiviral therapy is reserved for documented viral disease—there is no indication for empirical antiviral use. 1

Specific Indications for Antiviral Treatment:

• Herpes simplex or varicella-zoster lesions: Treat with acyclovir even if not the cause of fever, as these lesions provide portals of entry for bacteria and fungi during neutropenia 1
• Cytomegalovirus: Systemic CMV infections are uncommon in neutropenic patients except post-bone marrow transplantation; treat with ganciclovir or foscarnet when documented 1
• Respiratory viral infections: If identified early, use appropriate antivirals:
  • Ribavirin for respiratory syncytial virus 1
  • Zanamivir, oseltamivir, rimantadine, or amantadine for influenza 1

Preferred Agents for Herpesvirus Infections:

• Valacyclovir or famciclovir are preferred over oral acyclovir due to better absorption and longer dosing intervals 1

Long-Term Care Facility Residents

At the onset of suspected respiratory viral infection outbreaks in LTCFs, obtain nasopharyngeal wash or combined throat/nasopharyngeal swabs from several acutely ill residents for virus isolation and rapid diagnostic testing. 1

• Samples should be placed in refrigerated viral transport media and sent to experienced laboratories 1
• Focus testing on influenza A and other common respiratory viruses 1

Returned Travelers with Fever

Perform malaria films and rapid diagnostic tests in all patients who visited tropical countries within 1 year of presentation—three thick films/RDTs over 72 hours are needed to confidently exclude malaria. 1

• Viral hemorrhagic fever considerations: In high-risk patients, avoid unnecessary blood tests before consulting infectious diseases services 1
• Arboviral testing: Consider EDTA samples for PCR if features suggest arboviral infection 1
• HIV testing: Offer to all patients with pneumonia, aseptic meningitis/encephalitis, diarrhea, viral hepatitis, mononucleosis-like syndrome, unexplained lymphadenopathy, fever, or blood dyscrasia 1

Specific Viral Syndromes Requiring Treatment

Vesicular Lesions/Suspected Herpesvirus Infection

After obtaining appropriate samples, initiate acyclovir therapy immediately. 1

• Substitute ganciclovir only when there is high clinical suspicion of invasive cytomegalovirus infection 1

Suspected Viral Encephalitis

Lumbar puncture is mandatory; treat viral encephalitis with high-dose acyclovir. 1

Influenza in Hospitalized Patients

For confirmed influenza, administer oseltamivir 75 mg twice daily for 5 days in adults; treatment should begin within 48 hours of symptom onset. 2

• Pediatric dosing varies by weight and age 2
• Post-exposure prophylaxis: 75 mg once daily for 7 days in household contacts 2

COVID-19 with Severe Disease

For hospitalized patients requiring oxygen or mechanical ventilation, administer remdesivir 200 mg IV loading dose on Day 1, followed by 100 mg IV daily. 3

• Treatment duration: 5 days for non-ventilated patients; up to 10 days for those requiring mechanical ventilation/ECMO 3
• Perform hepatic laboratory testing before starting and during treatment 3

Critical Pitfalls to Avoid

• Do not use empirical antivirals in febrile patients without documented viral disease 1
• Do not routinely test blood for herpesviruses in immunocompetent ICU patients 1
• Do not use corticosteroids in patients with influenza pneumonia 4
• Do not administer live attenuated influenza vaccine within 2 weeks before or 48 hours after oseltamivir administration 2
• Do not discontinue evaluation for bacterial infection based solely on viral testing, as co-infections occur 1

Monitoring and Duration

• Assess response within 48-72 hours of initiating antiviral therapy 5
• If no improvement, re-evaluate for alternative diagnoses or resistant viral strains 5
• Continue treatment for the full recommended course even if symptoms improve 3, 2