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EBV, CMV and varicella serology

15 min

  • Call EBV infection recent or past from VCA IgM, VCA IgG, and EBNA antibody
  • Choose the CMV test for past exposure, current replication, or congenital infection
  • Choose lesion PCR or VZV IgG to tell current infection from past immunity

Read the full reference

Try first

Try first

A young adult's Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgG is reactive at a high value. What does that result establish by itself?

The next section explains it.

The next section explains it.

Right. The next section explains why.

The next section explains it.

Get the idea

EBV is dated by three antibodies together

EBV infects B cells, and the polyclonal B-cell response can produce heterophile antibodies. CDC advises against the rapid heterophile test for general use, because false-positive and false-negative results occur, especially in young children and early illness.1 EBV-specific antibodies give the clearer answer.

  • VCA IgM appears early and usually disappears within 4 to 6 weeks.
  • VCA IgG appears during the acute illness and persists for life.
  • EBNA antibody appears 2 to 4 months after onset and then persists.1
VCA IgMVCA IgGEBNA antibodyReading
NonreactiveNonreactiveNonreactiveNo past infection
ReactiveReactiveNonreactivePrimary infection
NonreactiveReactiveReactivePast infection

1

A high VCA IgG alone never dates the infection. Paired sera add little, because VCA antibodies are often present when the illness starts.1

CMV: the question picks the test

Cytomegalovirus (CMV) stays in the body after the first infection and can reactivate. Its tests answer different questions.

  1. Past exposure. CMV IgG. Donor and recipient IgG set a transplant's risk group.2
  2. Current replication. Quantitative CMV DNA by nucleic acid amplification test (NAAT) in plasma or whole blood. Serial results stay on one specimen type and one assay.2
  3. Congenital infection. Saliva polymerase chain reaction (PCR) within 3 weeks of birth, confirmed with urine PCR. Saliva is collected more than 1 hour after breastfeeding. Antibody testing cannot establish congenital CMV.3

CMV IgG stays reactive after past infection, so it cannot show replication. CMV IgM can persist, return with reactivation or react falsely.3

VZV: a lesion swab for now, IgG for the past

PCR on material from a skin lesion is the preferred test for current varicella-zoster virus (VZV) infection. Vesicle fluid, scabs and cells from the lesion base all work.4 VZV IgM has poor specificity and cannot separate primary infection from reinfection or reactivation. A reactive VZV IgG shows past varicella or vaccination and cannot confirm a current case.4

References
  1. Centers for Disease Control and Prevention. Laboratory testing for Epstein-Barr virus. April 10, 2024. Accessed September 27, 2026. https://www.cdc.gov/epstein-barr/php/laboratories/index.html
  2. Kotton CN, Kumar D, Manuel O, et al. The Fourth International Consensus Guidelines on the Management of Cytomegalovirus in Solid Organ Transplantation. Transplantation. 2025;109(7):1066-1110. doi:10.1097/TP.0000000000005374
  3. Centers for Disease Control and Prevention. Laboratory testing for CMV and congenital CMV. April 15, 2024. Accessed September 27, 2026. https://www.cdc.gov/cytomegalovirus/php/laboratories/index.html
  4. Centers for Disease Control and Prevention. Laboratory testing for varicella-zoster virus. May 10, 2024. Accessed September 27, 2026. https://www.cdc.gov/chickenpox/php/laboratories/index.html

Watch one

A 19-year-old college student has had fever, sore throat and swollen neck nodes for 10 days. His rapid heterophile test was negative. The EBV panel reads:

Does the panel support primary EBV infection?

TestResultPreviousReference intervalFlag
EBV VCA IgMReactiveNonreactive
EBV VCA IgGReactiveNonreactive
EBV EBNA antibodyNonreactiveNonreactive

Specimen: H 2, L 8, I 1. Serum

  1. VCA IgG is reactive, so he has been infected at some time.

    VCA IgG answers whether he has ever met EBV, and it opens the reading.

  2. VCA IgM is reactive, which points to a recent infection.

    VCA IgM is the early marker that fades within weeks.

  3. EBNA antibody is nonreactive, so the infection is less than about 2 to 4 months old.

    EBNA antibody forms months after onset, so its absence keeps the infection recent.

  4. The negative heterophile test does not outweigh the EBV-specific pattern.

    The heterophile test misses cases, especially early in the illness.

Yes. VCA IgM reactive with EBNA antibody nonreactive supports primary EBV infection, and the negative heterophile test does not change that.

Your turn

Problem 1 of 3

A lung transplant recipient is CMV IgG reactive. Her team wants to know whether CMV is replicating now. Which test answers that?

CMV IgG stays reactive after past infection. It cannot show whether the virus is replicating today.

Used CMV IgG to show current replication

CMV IgG remains after past infection, so a reactive IgG cannot show whether the virus is replicating now. Quantitative CMV DNA testing, kept to one specimen type and one assay, measures current replication. Reading IgG as activity can report replication that a DNA test would not find.

CMV DNA in blood measures current replication, and a quantitative result can be followed over time on the same assay.

CMV IgM can persist, return with reactivation or react falsely. It does not measure how much virus is present.

Saliva PCR is the screening test for congenital CMV in a newborn. Blood DNA testing follows replication after a transplant.

Hint
  1. Her IgG says she met CMV at some time.
  2. Sort the options into tests for antibody and tests for virus.

Review Cytomegalovirus

Problem 2 of 3

A 70-year-old man has a band of blisters on one side of his chest. Which specimen and test show current VZV infection?

VZV IgM has poor specificity and can appear in primary infection, reinfection and reactivation. A lesion swab answers directly.

Used VZV IgM to separate primary infection from reactivation

VZV IgM has poor specificity and can appear in primary infection, reinfection, and reactivation, so a positive IgM cannot date the infection. PCR on a lesion swab shows current infection.

VZV IgG shows past infection or vaccination. Most adults his age are IgG reactive whether or not VZV caused this rash.

Lesion PCR detects VZV DNA where the virus is active. It is the preferred test for current infection.

Hint
  1. Blood antibody reflects the whole history of his immune system.
  2. Ask which specimen could hold the virus that is causing this rash.

Review Varicella-zoster virus

Problem 3 of 3

A 24-year-old woman has had a sore throat for 1 week. Her results: VCA IgM nonreactive, VCA IgG reactive at a high value, EBNA antibody reactive. How does the panel read?

A high VCA IgG occurs in remote infection too. The reactive EBNA antibody places the infection months or years ago.

Dated EBV infection from a high VCA IgG

VCA IgG appears early and persists for life, and a high value occurs in recent and remote infection alike. Dating infection from it without VCA IgM and EBNA antibody can call a past infection recent.

VCA IgG with EBNA antibody and no VCA IgM fits an infection months or more in the past. EBV is unlikely to explain this week's sore throat.

A reactive VCA IgG shows she has been infected. The pattern tells when.

Paired EBV sera add little. This single panel already dates the infection.

Review Epstein-Barr virus

Use it

  • Dmitri Volkov, 52, received a kidney 7 weeks ago.
  • Before transplant he was CMV IgG nonreactive and his donor was CMV IgG reactive.
  • He now has fever. His CMV IgG is reactive today.
  • His earlier CMV DNA results were on plasma with the laboratory's usual assay.
  • Two days later a line of blisters appears on his right flank.
Decision 1 of 3

Does the reactive CMV IgG show that CMV is replicating?

New IgG shows he has now met CMV, which the donor organ could explain. It does not measure replication today.

Used CMV IgG to show current replication

CMV IgG remains after past infection, so a reactive IgG cannot show whether the virus is replicating now. Quantitative CMV DNA testing, kept to one specimen type and one assay, measures current replication. Reading IgG as activity can report replication that a DNA test would not find.

CMV DNA in blood measures the virus now. IgG only shows exposure.

CMV IgM can persist or react falsely. It does not measure replication either.

Review Cytomegalovirus

Decision 2 of 3

Plasma CMV DNA is 4,800 IU/mL. A whole-blood result from an outside laboratory last week was 2,100 IU/mL. How is the change read?

The two results come from different specimen types and assays. Their numbers are not comparable.

Serial CMV DNA results stay on one specimen type and one assay. Compare 4,800 IU/mL with his earlier plasma results.

No fixed conversion exists between specimen types and assays. The outside number cannot be adjusted into this one.

Review Cytomegalovirus

Decision 3 of 3

Which test do you suggest for the flank blisters?

VZV IgM appears in primary infection, reinfection and reactivation. It cannot tell them apart.

Used VZV IgM to separate primary infection from reactivation

VZV IgM has poor specificity and can appear in primary infection, reinfection, and reactivation, so a positive IgM cannot date the infection. PCR on a lesion swab shows current infection.

IgG shows past infection or vaccination. It cannot confirm a current case.

Lesion PCR detects VZV DNA in the rash itself.

Review Varicella-zoster virus

The clue that settled each question is what the result measures. IgG shows that he met a virus. DNA in blood or in a lesion shows the virus is present now.

Keep

Sources checked