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
Try first
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 IgM | VCA IgG | EBNA antibody | Reading |
|---|---|---|---|
| Nonreactive | Nonreactive | Nonreactive | No past infection |
| Reactive | Reactive | Nonreactive | Primary infection |
| Nonreactive | Reactive | Reactive | Past infection |
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.
- Past exposure. CMV IgG. Donor and recipient IgG set a transplant's risk group.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
- 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
- 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
- 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
- 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
- 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?
| Test | Result | Previous | Reference interval | Flag |
|---|---|---|---|---|
| EBV VCA IgM | Reactive | Nonreactive | ||
| EBV VCA IgG | Reactive | Nonreactive | ||
| EBV EBNA antibody | Nonreactive | Nonreactive |
Specimen: H 2, L 8, I 1. Serum
- 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.
- VCA IgM is reactive, which points to a recent infection.
VCA IgM is the early marker that fades within weeks.
- 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.
- The negative heterophile test does not outweigh the EBV-specific pattern.
The heterophile test misses cases, especially early in the illness.
Your turn
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.
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.
Results
- 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
To review
6 questions from this step will come back in Review.
Keep
Sources checked
The rest of this step
A short briefing, a demonstration at the bench, 3 practice problems and a short case.
A free account opens the rest and keeps your progress.