Cytomegalovirus - CMV

Cytomegalovirus (CMV) is a common infection. In the United States, nearly one in three children is infected by 5 years of age, and more than 50% of adults become infected by 40 years of age.  CMV can be transmitted in several ways: congenitally, by blood transfusion or organ transplantation, and through direct contact with bodily fluids, including urine, saliva, blood, genital secretions, and breast milk.  The virus may lie dormant or reactivate after the primary infection.  Although infected immunocompetent children and adults are generally asymptomatic, CMV can lead to serious complications in neonates, pregnant women, immunocompromised individuals, and those receiving transplants.  Polymerase chain reaction (PCR) testing is commonly used to detect and quantify viral load.  Serologic testing is most useful in immunocompetent individuals, in pregnant women with possible active infection, and during pretransplantation analysis.  

Quick Answers for Clinicians

Who should be tested for cytomegalovirus infection?
  • Immunocompromised patients who present with febrile illness, hepatitis, or colitis
  • Pregnant women with possible cytomegalovirus (CMV) infection
  • Neonates with congenital syndromes suggestive of CMV
  • Patients receiving organ transplants
Is routine cytomegalovirus screening recommended for pregnant women?

Maternal screening for primary cytomegalovirus (CMV) infection is not currently recommended in the United States.   

Which tests are available that detect cytomegalovirus infection?

Cytomegalovirus (CMV) can be detected by polymerase chain reaction (PCR), serology, viral culture, and histology. Quantitative PCR is generally the preferred test to detect CMV infection and guide posttransplantation therapy. 

Which tests are appropriate for monitoring cytomegalovirus infection?

A cytomegalovirus (CMV) by quantitative polymerase chain reaction (PCR) test is preferred for posttransplantation surveillance and to determine antiviral treatment response.  Refer to Monitoring.

How do I interpret serologic testing results?

Interpreting serologic test results can be challenging. A positive cytomegalovirus (CMV) immunoglobulin G (IgG) result suggests a past infection, but only in persons older than 1 year. A positive CMV IgM result cannot be used alone to diagnose primary CMV infection. See the CDC’s suggested interpretive guidance. 

Indications for Testing

CMV is a common virus. Most people with this infection have no symptoms. However, the following populations warrant consideration for laboratory testing:

  • Immunocompetent patients who present with mononucleosis-like illness and have tested negative for Epstein-Barr virus (EBV) 
  • Immunocompromised patients who present with febrile illness, hepatitis, or colitis 
  • Pregnant women with possible active CMV infection (infection immediately before or during the first trimester of pregnancy increases the risk of cytomegalic inclusion disease in the fetus) 
  • Neonates with congenital syndromes (eg, hepatosplenomegaly, microcephaly, sensorineural deafness) suggestive of CMV 
  • Patients receiving organ transplants 

Laboratory Testing

Diagnosis

Immunocompromised Individuals

Molecular testing (eg, quantitative PCR) for viral DNA is preferred for detecting CMV infection because it:

  • Quantifies viral load
  • Provides rapid and early detection
  • Offers higher sensitivity than culture 

PCR quantitative testing is used both before and after organ transplantation to test for CMV status.  Serologic testing is not recommended for diagnosis in this population.

Pregnant Women

Serologic assays are the main tests used to evaluate pregnant patients for primary CMV infections. Testing for maternal CMV infection generally occurs after concerning ultrasound findings.  For women with possible primary CMV infections during pregnancy, diagnosis should be based on either immunoglobulin G (IgG) seroconversion testing or positive CMV IgM and IgG with low IgG avidity testing. 

Interpretation of CMV Serology Test Results
CMV IgG positive

Suggests past infection

Only applicable for persons ≥12 mos of age (when maternal antibodies are no longer present)

Paired CMV IgG samples (taken 1-3 mos apart)

Can be used to diagnose primary infection

Seroconversion (initial IgG-negative sample followed by positive second sample) offers clear evidence for recent primary infection

CMV IgM positive In isolation, not helpful to diagnose primary CMV infection because IgM can also be present during recurrent CMV infection
Source: CDC, 2020 

CMV IgG avidity testing aids in distinguishing between primary and recurrent CMV infection in pregnant women after initial serologic testing.

Interpretation of CMV IgG Avidity Test Resultsa
Low IgG avidity

Suggests primary CMV infection occurred within the last 2-4 mos

During first trimester, patients should seek consultation with obstetrician experienced with congenital CMV infections; further invasive testing may be warranted

Intermediate IgG avidity

Clinical relevance undetermined

Lower risk of intrauterine transmission

High IgG avidity Suggests past infection

aBecause not all avidity assays have been validated, they should be interpreted with caution.

Source: CDC, 2020 

CMV can be detected in the amniotic fluid of infected fetuses by either culture or PCR.  PCR testing of amniotic fluid is most sensitive at >21 weeks gestation. The detection of CMV in amniotic fluid does not predict the severity of congenital CMV infection. 

Neonates

PCR testing of saliva can also identify CMV infection. Following positive results, PCR testing of urine is used for confirmation (most seropositive mothers shed CMV in breast milk, which can lead to a false-positive saliva test result in a recently breastfed infant).  Refer to the CDC website for information on testing for congenital CMV infection in newborns. 

Immunocompetent Individuals

Most healthy individuals who acquire CMV after birth experience few disease symptoms and no long-term health consequences. Infected individuals may present with mononucleosis-like symptoms.  CMV-induced mononucleosis can be symptomatically indistinguishable from EBV-induced mononucleosis.  EBV is most often the causative agent, but CMV might be considered in the differential diagnosis if a negative heterophil antibody test rules out EBV mononucleosis.  In most patients, CMV IgM antibodies will be positive during the symptomatic phase of the disease.  However, IgM antibodies may not peak until 4-7 weeks into the infection and may remain elevated for up to 1 year or longer. IgG antibodies should continue to increase at least fourfold during active infection.  Therefore, in an otherwise healthy patient in whom EBV has been ruled out, it is not necessary to repeat a CMV IgM test if a previous IgM test result was positive.

Monitoring

PCR quantitative testing is used to monitor individuals at risk of developing CMV after solid organ or hematopoietic stem cell transplantation.    Quantitation of CMV viral load in plasma correlates with progression of disease. Monitor according to site-specific transplantation protocols.

ARUP Laboratory Tests

Quantitative PCR

Preferred test to detect, quantify, and monitor CMV infection

 

Use to determine antiviral drug resistance

Qualitative PCR

Detects CMV but does not quantify viral load; potentially useful for specimens other than blood

Serology

Primary test to discriminate between current and past CMV infection in immunocompetent individuals

Use to distinguish between primary and recurrent CMV infection in pregnant women after initial serologic testing

Rapid Culture
Generally not recommended (molecular methods preferred)

Medical Experts

Contributor

Couturier

Marc Roger Couturier, PhD, D(ABMM)
Professor of Pathology (Clinical), University of Utah
Medical Director, Parasitology/Fecal Testing, Infectious Disease Antigen Testing, Bacteriology, and Molecular Amplified Detection, ARUP Laboratories
Contributor

Jackson

Brian R. Jackson, MD, MS
Associate Professor of Pathology (Clinical); Adjunct Associate Professor, Biomedical Informatics, University of Utah
Medical Director, Support Services, IT, and Business Development, ARUP Laboratories

References

Additional Resources