What labs should I order to rule out Cytomegalovirus (CMV)?

Laboratory Testing to Rule Out CMV Infection

For immunocompetent patients, order CMV IgM and IgG antibodies as the first-line test; for immunocompromised patients or transplant recipients, order CMV DNA quantitative PCR (viral load) instead of serology. 1

Testing Strategy Based on Patient Population

Immunocompetent Patients

Order CMV-specific antibody testing (IgM and IgG) from serum as your initial diagnostic approach. 1

• CMV IgM positive indicates recent/acute infection 1
• CMV IgG positive alone indicates past exposure only, not active infection 1, 2
• Both negative effectively rules out CMV infection 1

Critical caveat: False-positive CMV IgM results occur frequently in patients with:

• Epstein-Barr virus (EBV) infection 1, 3
• Systemic lupus erythematosus or other autoimmune conditions with activated immune systems 3
• Other causes of immune activation 1, 3

If clinical suspicion remains high despite negative or equivocal serology, proceed to CMV DNA PCR testing. 1

Immunocompromised Patients (Transplant Recipients, HIV, Chemotherapy)

Do not rely on antibody testing—order CMV DNA quantitative PCR (viral load) from whole blood or plasma. 1, 2

• CMV viral load by nucleic acid amplification test (NAAT) is the preferred diagnostic and monitoring tool 1, 2
• Antigenemia testing (pp65 antigen) is an alternative but is being replaced by NAAT at most centers 1, 4
• Viral load testing provides more reliable evidence of active infection than serology in immunocompromised hosts 3, 2
• Sensitivity and specificity exceed 90% for detecting active CMV infection 4
• Quantitative results guide preemptive therapy decisions and monitor treatment response 1

Specimen requirements: Collect whole blood, peripheral blood lymphocytes, or plasma in EDTA tube, room temperature, transport within 2 hours. 1

Pregnant Women with Suspected CMV

Order CMV IgM and IgG antibodies initially. 5

• If IgM positive and IgG positive, order IgG avidity testing to distinguish primary from non-primary infection 2, 6
  • Low avidity = recent primary infection (higher fetal risk) 6
  • High avidity = past infection or reinfection (lower fetal risk) 6
• Critical limitation: A negative CMV IgM in the second trimester does NOT exclude congenital CMV infection 6
• If fetal abnormalities are detected on ultrasound, proceed to amniocentesis with CMV PCR on amniotic fluid regardless of maternal serology 5, 6

Neonates (Suspected Congenital CMV)

Collect urine or saliva for CMV culture or CMV DNA PCR within the first 21 days of life. 5, 7

• Urine culture remains the gold standard for diagnosing congenital CMV 7
• Saliva PCR is being assessed as a useful screening method 7
• Testing must occur within 21 days of birth to distinguish congenital from postnatal infection 5
• Dried blood spot PCR lacks sufficient sensitivity for universal screening 7

Site-Specific Testing for CMV Disease

When CMV end-organ disease is suspected, order CMV DNA PCR from the affected site:

• CNS disease: CMV DNA PCR from cerebrospinal fluid 1
• Pneumonitis: CMV DNA PCR from respiratory specimens (BAL) 1
• Colitis: CMV DNA PCR and/or immunohistochemistry on colon biopsy tissue 1
• Any tissue biopsy: CMV immunohistochemistry or in situ hybridization on formalin-fixed, paraffin-embedded tissue 1

Specimen handling: Collect in sterile container, room temperature, transport within 2 hours. 1

Common Pitfalls to Avoid

• Do not use serology alone in immunocompromised patients—viral load testing is essential 1, 2
• Do not assume negative IgM rules out CMV in pregnancy—fetal infection can occur with maternal reactivation or reinfection 6
• Do not misinterpret positive IgG alone as active infection—this only indicates past exposure 2
• Do not delay amniocentesis in pregnant women with fetal abnormalities based on negative maternal IgM 6
• Do not order CMV culture for rapid diagnosis—turnaround time is 1-14 days with poor sensitivity 1