Clinicians should obtain serum to store for future serologic testing when viral pathogens are considered as the potential cause of a critical illness.
Multiplex polymerase chain reaction panels are increasingly used to diagnose viral infections from various specimens, for example, respiratory, cerebrospinal fluid, and stool.
Current treatment for most viral infections remains supportive, with antiviral therapy generally limited to treatment of herpes and some respiratory viruses.
Providers should initiate empiric treatment with acyclovir rapidly when herpes simplex virus encephalitis or neonatal disease is suspected.
Parainfluenza and influenza viruses are often associated with bacterial coinfections.
Infection control precautions should be initiated early to prevent spread of infection to staff and other patients when viral pathogens are suspected.
Viral infections are a frequent cause of disease in individuals of all ages. In general, the spectrum of illness is varied, with young and/or immunosuppressed children at higher risk of severe disease. This chapter covers viral causes of entities commonly seen in the intensive care unit (ICU): myocarditis, hepatitis, pneumonitis, and meningitis/encephalitis, as well as certain emerging infections that may require critical care ( Table 108.1 ). This content is focused on providing the reader with guidance for the initial management of patients with viral infections, with an emphasis on diagnosis and therapy.
|Arboviruses (arthropod-borne viruses)||XX||XX|
|Western equine encephalitis virus||X||X|
|Eastern equine encephalitis virus||X|
|St. Louis encephalitis virus||X||X|
|California encephalitis virus (La Crosse)||X||X|
|Colorado tick fever||X||X|
|West Nile encephalitis virus||X|
|Coronaviruses (OC43, 229E, HKU1, NL63, SARS, and MERS)||XX|
|X||X b||X a||XX||XX||X|
|X a||XX a||X||X||X|
|Lymphocytic choriomeningitis virus||X||X||X|
|Parainfluenza virus types 1, 2, 3, 4||XXX|
|Parvovirus B19 c||XX|
Five primary methods are used to diagnose viral infections: (1) serologic detection of an early antibody (immunoglobulin M [IgM]) or a fourfold or higher rise in IgG antibody titers between acute phase and convalescent phase (at least 10–14 days later) serum; (2) observation of characteristic cytopathic effect in cell culture; (3) microscopic identification of viral inclusion bodies; (4) assays that link specific antibodies to viral antigens (complement fixation, neutralization, immunofluorescence assays, enzyme-linked immunosorbent assay [ELISA]); and (5) molecular techniques that amplify and quantify viral deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). The latter are increasingly being used in panels of multiple pathogens for various samples, including respiratory, stool, and cerebral spinal fluid (CSF). If a viral infection is suspected, acute-phase serum should be held for later interpretation. It is critical that this specimen is drawn before administration of intravenous immunoglobulin (IVIG) or blood products. Samples for viral cultures and polymerase chain reaction (PCR) testing should be collected from the appropriate sites with specific swabs. Nasal swabs and swabs of the base of a vesicle or ulcer (for varicella zoster virus [VZV], herpes simplex virus [HSV]) should include good cellular content to improve the sensitivity of the assay. Table 108.2 outlines appropriate samples and testing for a number of specific viral pathogens.
|Viral Agent||Specimen||Recommended Diagnostic Tests a|
|Adenovirus||NP, BAL fluid||PCR|
|Arboviruses (California encephalitis, Colorado tick fever, EEE, SLE, WEE, West Nile) c||Serum/plasma||IgM and IgG antibody, d PCR|
|CSF||IgM e and IgG antibody, d PCR|
|Chikungunya virus c||Serum/plasma||PCR, IgM and IgG antibody d|
|Coronaviruses (OC43, 229E, HKU1, NL63, SARS, and MERS) c , f||NP aspirate (preferred for SARS/MERS) or swab, OP swab, BAL, stool (SARS/MERS), tissues (SARS/MERS)||PCR|
|Serum/plasma (SARS/MERS)||PCR, IgM and IgG antibody|
|Ebola virus c||Whole blood, oral secretions||PCR|
|Enteroviruses (echoviruses, coxsackie viruses, enteroviruses) c||CSF, NP, pharynx||PCR|
|Serum/plasma b||PCR (enterovirus D68 may not be detected by these methods)|
|Hantavirus c||Serum||IgM and IgG antibody d|
|Tissue (lung, kidney, spleen preferred; antemortem—lung or bone marrow)||PCR, immunohistochemistry|
|Hepatitis viruses||Serum||Serology for all|
|Hepatitis A virus (HAV)||Serum||Anti-HAV IgM|
|Hepatitis B virus (HBV)||Serum/plasma b||HBsAg, anti-HBcAb IgM, PCR|
|Hepatitis C virus (HCV)||Serum/plasma||Anti-HCV IgG, PCR|
|Hepatitis E virus (HEV)||Serum/plasma b||Anti-HEV IgM, PCR|
|CMV||NP or BAL||Shell vial or rapid culture, PCR i|
|Tissue||IgM and IgG antibody d|
|EBV||Serum||Viral capsid antibody (VCA) panel or slide agglutination test (Monospot)|
|HHV-6B||Serum/plasma, b CSF||PCR|
|HSV types 1 and 2||CSF, serum/plasma b||PCR|
|Base of lesion, NP, conjunctiva, tissue||PCR, culture|
|Serum||IgG antibody d|
|VZV||Base of lesion, tissue||PCR, FA, and culture|
|Serum||IgM and IgG antibody d|
|Serum/plasma, b CSF||PCR|
|Influenza types A and B||NP, pharynx, BAL fluid||PCR|
|LCMV c||Serum/plasma b||PCR, IgM, and IgG antibody d|
|Measles (rubeola) c||Serum||IgM and IgG antibody d|
|Urine, blood, NP||PCR|
|SSPE||CSF||Oligoclonal bands, IgG|
|Metapneumovirus||NP, BAL fluid||PCR|
|Mumps c||Buccal swab, saliva||PCR|
|Serum||IgM and IgG antibody d|
|CSF, pharynx, saliva||PCR|
|Parechoviruses||CSF, serum/plasma, b NP, stool||PCR|
|Parainfluenza viruses||NP, BAL fluid, tissue||PCR|
|Parvovirus||Serum/plasma b||PCR, IgM and IgG antibody d|
|BK virus||Serum, urine, CSF||PCR|
|JC virus c||Brain biopsy, h CSF||PCR|
|Rabies virus c||Serum, CSF||Rabies-specific antibody by neutralization assay|
|Saliva, brain, tissues, urine||PCR|
|Punch biopsy (nape of neck), brain||Direct fluorescent antibody (DFA; consult ID)|
|HIV||Serum||HIVAg/Ab combination immunoassays|
|Whole blood||RNA/DNA PCR|
|Plasma, CSF||RNA PCR|
|HTLV||Serum, CSF||Anti-HTLV antibodies|
|Whole blood, tissue||PCR|
|Rotavirus||Stool||PCR, EIA, or latex particle agglutination assays|
|RSV||NP, BAL, tissue||PCR, DFA, IA|
|Rubella c||Serum||IgM and IgG antibody d|
|NP, CSF, urine||PCR|
|SARS-CoV-2||Serum||IgM and IgG antibodies|
|NP, stool, sputum||PCR|
a Multiple diagnostic tests are available for each pathogen. Commonly recommended diagnostic tests are listed; however, if results are negative or specimens are not available, infectious disease consultation may be helpful for additional or special testing.
c Pathogen may have significant public health implications. Testing should be performed in consultation with infectious disease and/or local public health department (for enteroviruses, if enterovirus 68/71 suspected). Testing is often not available without assistance of the Public Health Department, and recommended specimens and tests are frequently evolving; see www.cdc.gov for updates.
d IgM and IgG antibody may also be referred to as “serology” on laboratory request forms. For most viral pathogens, when testing for IgG, it is optimal to collect acute and convalescent sera approximately 4 weeks apart.
f For suspected SARS or MERS, specimens should be collected from several locations at different time points following symptom onset. See www.cdc.gov/sars/clinical/index.html for updated diagnostic information.
i Because shedding of CMV occurs in the lungs of seropositive stem cell transplant recipients without overt CMV disease, the recovery of CMV DNA by PCR from BAL fluid (which is considerably more sensitive than culture) without shell vial or culture positivity is of uncertain significance. Thus, PCR testing for CMV DNA in BAL or biopsy fluid should not be ordered routinely.
In general, for most life-threatening viral infections, the primary treatment is supportive. Because of improvements in intensive medical care, death from these illnesses has decreased even without the availability of specific antiviral therapy. Although lacking for many infections, there are antivirals for most of the herpes group viruses and some respiratory viruses. For most infections, the efficacy of antiviral therapy is decreased if therapy is delayed. Thus, early diagnosis and rapid initiation of medication are essential. Consultation with an infectious disease specialist is recommended because some antiviral agents are not commercially available and new treatment modalities continue to be identified. A listing of antiviral agents, indications, and dosages is provided in Table 108.3 .
|Virus||Drug of Choice/Dose a||Alternate Agents/Dose|
|Adenovirus||No currently approved therapy||Cidofovir may be considered for immunocompromised patients with disseminated disease or severe pneumonia. ,|
|Coronavirus||No currently approved therapy|
|Enterovirus||No currently approved therapy|
|Hantavirus||No currently approved therapy|
|Foscarnet (90 mg/kg q12h × 2–3 wk, then 90 mg/kg q24h), cidofovir (5 mg/kg/wk; high risk of renal toxicity, use with probenecid and saline hydration) in children >2 years.|
|Acyclovir (20 mg/kg/dose IV q8h) for encephalitis in neonates and children <12 y and for neonates with disseminated disease; 10 mg/kg/dose IV q8h for children >12 y.||No specific dosing recommendations are available for HSV-associated hepatitis and pneumonitis. At least 10 mg/kg/dose should be considered outside the neonatal period.|
|No currently approved therapy||Foscarnet and ganciclovir have in vitro activity. Case reports and series show variable clinical response with one or both drugs in combination.|
|Acyclovir (10–12 mg/kg/dose IV q8h); high-dose acyclovir (10 mg/kg/dose) could be used for VZV encephalitis or for disease in immunocompromised children.|
|Influenza A/B||Oseltamivir b or zanamivir (≥5 y) 10 mg (2 oral inhalations) q12h × 5 days or peramivir IV (≥2 y) 12 mg/kg dose, up to 600 mg maximum × 1 dose for uncomplicated influenza. Baloxavir (≥12 y) 40 to <80 kg: one 40-mg dose; >80 kg: one 80-mg dose for uncomplicated influenza.||Rimantadine or amantadine. Generally not recommended due to widespread resistance. Combination empiric therapy may be indicated for severely ill immunosuppressed patients. ,|
|JCV||No effective therapy||In HIV infection, treatment with combination antiretroviral therapy may improve survival. Potential role for cidofovir.|
|Metapneumovirus||No currently approved therapy||Case reports suggest that ribavirin and IVIG may be used successfully in immunosuppressed patients. ,|
|Parechoviruses||No currently approved therapy|
|Parainfluenza virus||No currently approved therapy|
|RSV||Aerosolized ribavirin (2 g reconstituted in 33 mL tid) × 5 d has been used with modest efficacy in patients with severe RSV pneumonia and in immunocompromised patients ; not recommended for uncomplicated disease or in otherwise healthy subjects.||Oral ribavirin may improve outcomes of RSV pneumonia in immunocompromised and high-risk patients but data are limited in pediatrics. ,|