Epstein-Barr virus (EBV)

Sequential testing (EBNA first)

Not immune Acute infection Transient phase** Past infection
VCA IgM - + + -
VCA IgG - +* + +
EBNA-1 IgG - - + +

* Can be negative in very early phase of acute infection
** Indeterminate infection stage. Requires additional testing. Same result constellation can be observed during reactivation of infection.

Adapted from:

  1. Hess R. Routine Epstein-Barr virus diagnostics from the laboratory perspective: still challenging after 35 years. J Clin Microbiol. 2004;42:3381-7.
  2. Middeldrop JA. Epstein-Barr virus-specific humoral immune responses in health and disease. In: C. Münz (ed.), Epstein Barr Virus Volume 2, Current Topics in Microbiology and Immunology 391, pp. 289-322. Springer International Publishing. Switzerland; 2015.
  3. De Paschale M and Clerici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions. World J Virol. 2012;1:31-43.
  4. Public Health England (PHE). UK Standards for Microbiology Investigations. Epstein-Barr virus serology. Virology. 2019;26(6):2-8. [Internet; updated 2019 Jan 24; cited 2024 Mar 4]. Available from: https://www.gov.uk/government/publications/smi-v-26-epstein-barr-virus-serology.
  5. Rea TD, Ashley RL, et al. A Systematic Study of Epstein-Barr Virus Serologic Assays Following Acute Infection. Am J Clin Pathol. 2002;117:156-61.
Product Description Tests Product page
Elecsys® EBV IgM a) Qualitative detection of IgM class antibodies to EBV in human serum and plasma 100
Elecsys® EBV IgM b) 300
Elecsys® EBV VCA IgG a) Qualitative detection of IgG class antibodies to EBV, including VCA, in human serum and plasma 100
Elecsys® EBV VCA IgG b) 300
Elecsys® EBV EBNA IgG a) Qualitative detection of IgG class antibodies to EBV EBNA-1 in human serum and plasma 100
Elecsys® EBV EBNA IgG b) 300

a) for use on the cobas® e 411 analyzer and the cobas® e 601 / 602 modules;
b) for use on the cobas® e 402 and cobas® e 801 analytical units

* In a small number of cases EBV EBNA-1 IgG may be detectable early (10 days after the onset of illness in <5 %)3.

VCA IgM VCA IgG EBNA-1 IgG Interpretation
- - - Seronegative, no immunity
+ - - Presumed early phase of infection#
+ + - Acute infection
+ + + Transient phase of primary infection, or reactivation#
- + + Past infection
- + - Isolated VCA IgG#
- - + Isolated EBNA-1 IgG#
+ - + Implausible result#

Note: EBV serology is not recommended to diagnose immunocompromised individuals.
# Indeterminate EBV serology. Additional testing required.

Adapted from:

  1. De Paschale M and Cleirici P. Serological diagnosis of Epstein-Barr virus infection: Problems and solutions. World J Virol. 2012;1:31-43.
  2. De Paschale M, Agrappi C, et al. Seroepidemiology of EBV and Interpretation
    of the ‘‘Isolated VCA IgG’’ Pattern". J Med Virol. 2009;81:325-331.
  3. De Paschale M, Cagnin D, et al. Significance of the “isolated EBNA-1 IgG”
    pattern in past EBV infection. Micro Med. 2009;24:51-52.
  4. Public Health England (PHE). UK Standards for Microbiology Investigations. Epstein-Barr virus serology. Virology. 2019;26(6):2-8. [Internet; updated 2019 Jan 24; cited 2024 Mar 4]. Available from: https://www.gov.uk/government/publications/smi-v-26-epstein-barr-virus-serology.
  5. Henle G, et al. Antibodies to Epstein-Barr virus-associated nuclear antigen in infectious mononucleosis. J Inf Dis. 1974;130:231-9.
  • Step 1
  • Step 2
  • Step 3
Step 1

Perform EBNA-1 IgG test

EBNA-1 IgG test
  • Step 1
  • Step 2
  • Step 3
Step 2

Perform VCA IgM and VCA IgG tests

VCA IgM test
VCA IgG test
  • Step 1
  • Step 2
  • Step 3

Summary

Past infection
In a small number of cases EBV EBNA-1 IgG may be detectable early (10 days after in onset of illness in <5 %)

  • Step 1
  • Step 2
  • Step 3

Summary

Seronegative, no immunity.

  • Step 1
  • Step 2
  • Step 3

Summary

Isolated VCA IgG.

This constellation may be found in cases of past infection with the loss or disappearance of EBNA-1 IgG, or in cases of acute infection with the delayed or early disappearance of VCA IgM.

This serological profile is considered indeterminate and is observed in approximately 7% of laboratory routine testing. Additional testing is required to distinguish transient infection and reactivation, including:

  • Immunoblots for IgG, based on recombinant antigens

  • IgG avidity: low avidity indicates recent infection (<12 weeks after symptom onset)

  • EBV DNA testing: the presence of EBV DNA in plasma/serum is considered a sign of primary infection. 

  • Heterophilic antibodies and anti-EA (D) IgG, both commonly found in acute infection, but not very sensitive or specific.

  • Serial testing (after about 30 days) to observe changes in antibody profiles

  • Step 1
  • Step 2
  • Step 3

Summary

Presumed early phase of infection.

This constellation usually indicates an early stage of acute infection, but can also occur due to unspecificity of the VCA IgM test  (interferences or cross-reactivity).   

This serological profile is considered indeterminate and additional testing is required to confirm acute infection, including:

  • Potential interfering or cross-reacting factors (e.g. Rheumatoid factor, autoantibodies, CMV, Parvovirus B19) in case of an isolated VCA IgM profile

  • Immunoblots for IgM, based on recombinant antigens

  • EBV DNA testing

  • Heterophilic antibodies and anti-EA (D) IgG, both commonly found in acute infection, but not very sensitive or specific.

  • Serial testing (after about 30 days) to observe changes in antibody profiles

  • Step 1
  • Step 2
  • Step 3

Summary

Acute infection.

Back
Next Restart simulation
Step
Result
Interpretation
1
EBNA-1 IgG = ...
waiting for input
1
EBNA-1 IgG = negative

Presumed seronegative or acute infection.

1
EBNA-1 IgG = positive
Past infection.
2
VCA IgM test = ...
VCA IgG test = ...
waiting for input
2
VCA IgM test = negative
VCA IgG test = negative
Seronegative, no immunity.
2
VCA IgM test = negative
VCA IgG test = positive
Isolated VCA IgG.
2
VCA IgM test = positive
VCA IgG test = negative
Presumed early phase of infection.
2
VCA IgM test = positive
VCA IgG test = positive
Acute infection.
End of test sequence