The Epstein-Barr Virus (EBV) test is often used to diagnose people suffering from symptoms of mononucleosis. Read on to discover what an abnormal result means and how to tell if you have a current or past infection.
Epstein-Barr Virus Basics
The Epstein-Barr virus (EBV), or human herpesvirus 4, is one of eight types of herpes viruses that are known to infect humans. EBV is extremely common: it is estimated that up to 90% of adults worldwide carry the virus [1, 2].
The virus usually does not cause any symptoms in children. However, between 30-50% of adolescents and adults who have the virus will develop infectious mononucleosis (mono) [2].
Because EBV is spread through saliva, mono has earned the nickname “the kissing disease.” It causes sore throat, fatigue, and fever, among other symptoms [3].
EBV can increase the risk for certain cancers and immune system disorders and has been linked to multiple autoimmune disorders [4, 5, 6, 7, 8].
What is the Epstein-Barr Virus Test?
The Epstein-Barr virus test is a blood test that determines if your body is producing antibodies and mounting an immune response against EBV [2]. It is also known as the Epstein-Barr virus antibody profile.
If you have the virus, your body will produce different types of antibodies to help combat the infection. These antibodies circulate in your blood and can be detected with the EBV test [2].
By revealing which types of antibodies you have, the test can determine if you have a current or a past infection [2].
About 70% of people tested will have antibodies indicative of past infections [9].
After your body successfully fights the virus, it remains dormant in your cells and doesn’t cause any symptoms. However, it can be reactivated by stress or a weakened immune system [10].
When is it Ordered?
Your doctor will order an Epstein-Barr virus test if they suspect that you have mono. Symptoms to watch for include [11]:
- Sore throat
- Swollen lymph glands
- Fatigue
- Headache
- Poor appetite
- Fever
Symptoms of mono usually last 2 to 3 weeks, though certain symptoms such as fatigue and muscle pain may last longer [3, 12].
Because the disease is most common in young adults between the ages of 15 and 24, your doctor may take your age into account when deciding whether to order the test [13].
Procedure
To test for EBV-specific antibodies, you will need to get your blood drawn. Results usually take a few days to come back.
Monospot test is a more rapid test that can give you results within minutes. For this test, you may also need to have your blood drawn. However, in most commercially-available tests, you will only need to give a small blood sample from a finger prick [14].
Within the first week of symptoms, the monospot test may give you a false-negative result. If the initial result is negative and your doctor still suspects mono, he may ask you to repeat the test a week or so later [13].
Types of Epstein-Barr Tests
EBV-Specific Antibody Tests
Your immune system produces antibodies against different parts, or antigens, of EBV. The type of antibodies that are detected in your blood helps your doctor determine if you have a current or past infection [9].
VCA IgG antibody (EBV AB VCA IgG)
Viral capsid antigen (VCA) IgG antibodies are directed against the protein shell (capsid) of the virus. These antibodies typically appear at the same time as infection symptoms [2].
Once they are made, VCA IgG antibodies will stay in your blood for life. This means they will always be detectable, even if you are not suffering from a current infection [15].
This also means that, by themselves, they are unhelpful in determining if you have a current or past infection.
IgG Avidity Test
In some cases where a clear diagnosis can’t be made, the IgG avidity test may be used. It measures how mature VCA IgG antibodies are by seeing how strongly they bind to EBV antigens [2].
During the early stages of an infection, VCA IgG antibodies are immature and don’t bind as strongly to EBV antigens. As the infection progresses, they start to develop and mature [2].
This makes the avidity test useful for estimating how long the infection has lasted as well as determining if it’s a current or past infection [2].
VCA IgM antibody (EBV AB VCA IgM)
VCA IgM antibodies are also directed against the virus shell and usually appear at the same time as VCA IgG antibodies. However, unlike VCA IgG antibodies, they disappear within a few weeks [16, 17].
In some cases, VCA IgM antibodies may be detectable for several months [18].
They are found in up to 75% of people with mono [19].
Epstein-Barr Nuclear Antigen Antibody (EBNA)
Epstein-Barr nuclear antigen (EBNA) antibodies are directed against proteins that the virus uses to survive and replicate its DNA after it enters into a dormant phase [20, 2, 21].
EBNA antibodies are only detectable 3-4 weeks after the onset of symptoms, after mono has run its course and the virus is no longer active. In most cases, they stay in circulation for life and are a sign of a past infection [2, 9].
Early Antigen Antibody (EBV EA)
Epstein-Barr early antigen antibodies (EA) are directed against proteins that control how the protein shell (capsid) of the virus is made [22].
Like their name suggests, they are found in the first 3-4 weeks of the infection and are no longer detectable after 3-4 months in most people [2, 23].
In some cases, they may be detectable for years after the initial infection [2].
EA antibodies are also detected in people who have a reactivated infection or in cases of certain cancers linked to EBV [23].
They are not usually tested for in routine practice, but they may be used in cases where a diagnosis can’t be made using VCA or EBNA antibodies [2].
Monospot Test
The EBV-specific antibody test is the gold standard when it comes to diagnosing mono. However, it usually takes a few days for the results to come back [14].
With an illness like mono, which is short-lived and has symptoms very similar to those of other illnesses, time is of the essence. Diagnosing it quickly can help reduce complications and prevent the use of unnecessary treatments such as antibiotics [14].
The heterophile antibody monospot test (more commonly known as just “monospot test”) was developed to deliver rapid results within 5 to 10 minutes [14, 2].
It’s also cheaper and only requires a blood sample from a finger prick [14, 2].
The test detects the presence of antibodies in the blood called heterophile antibodies, which are made in response to EBV infection. Unlike EBV-specific antibodies, they are not unique to EBV and will also bind to other antigens, including cells of other animal species [2].
In fact, most monospot tests use sheep, goat, or horse red blood cells to detect the presence of heterophile antibodies. When these cells are added to a blood sample they will bind to any heterophile antibodies present. When this occurs, the sample “clumps” together, yielding a positive result [2].
Heterophile antibodies peak 2-5 weeks after symptoms begin and then decline rapidly [2].
The monospot test does have some drawbacks, the biggest being the relatively high frequency of false-negative results. In other words, even if you are infected with EBV, there is a good chance the test will give you a negative result [14].
On the other hand, a positive result almost always means you have an infection.
The CDC does not recommend using the monospot test to diagnose mono due to its poor accuracy [14].
In cases where the monospot test is negative but the doctor still suspects mono, further testing using the EBV-specific antibody test may be required [24].
Complete Blood Count
A complete blood count (CBC) is frequently ordered alongside the monospot test to help confirm a positive result or, in the case of a negative result, and to determine if further tests are needed [24].
The CBC will tell you whether specific white blood cells called lymphocytes are elevated, which is commonly the case with mono [24].
It will also reveal if a subset of large lymphocytes called atypical lymphocytes is also elevated. Atypical lymphocytes greatly increase in response to viral infections such as mono [12].
Result Interpretation
Normal Result
A normal result means that the test did not find any antibodies in your blood. In the case of the EBV-specific antibody test, a negative result likely means that you have never been infected with EBV [24].
In the case of the monospot test, a negative result may mean that you are still in the early stages of the infection and that the test will have to be repeated [24].
There are a few other viruses and parasites that can cause mono. If you are experiencing symptoms of mono and your EBV test results come back normal, you may need additional tests to identify the cause [2].
Abnormal Result
An abnormal result means that the test has found antibodies to EBV in your blood. This means that you are currently infected with EBV or have been infected in the past.
Like any lab test, false-positives and false-negatives can occur. For example, an acute infection with another herpesvirus called cytomegalovirus or the parasite Toxoplasma gondii can cause a false-positive VCA IgM result [25].
Your doctor will interpret your results in conjunction with your symptoms, medical history, and other test results.
Below is a table displaying the most common combinations of results from the EBV-specific test and their interpretations [25].
| Interpretation | Antibodies | ||
| VCA IgG | VCA IgM | EBNA IgG | |
| No Infection | − | − | − |
| Current Acute Infection | + | + | − |
| Past Infection | +/− | − | + |
| Late Acute OR Reactivated Infection | + | + | + |
Levels of antibodies detected in the blood, called titers, can’t tell how long you’ve had the infection or how severe it is.
Sometimes, doctors are unable to make a diagnosis given the antibody pattern. This occurs when a person has the following results [2]:
- Positive for VCA IgG and negative for both VCA IgM and EBNA
- Positive for VCA IgM and negative for both VCA IgG and EBNA
- Positive for EBNA and negative for both VCA IgG and VCA IgM
- Positive for all three antibodies (further testing required to determine whether the infection is late acute or reactivated)
If you have any of these antibody patterns, your doctor will usually do further testing. They may check IgG avidity test, the EA antibody test, or another test that detects the presence of DNA belonging to EBV [2].
Acute vs. Chronic Infection
Acute
An acute EBV infection, also called a primary infection, causes mono. The associated symptoms usually resolve within weeks of catching the virus; however, some symptoms may last longer [11, 13].
After the symptoms go away, the virus is contained and enters a dormant phase wherein it stops reproducing itself and spreading.
Chronic
Chronic active EBV disease (CAEBV) is a rare disorder in which a person is unable to successfully fight and contain the virus [26].
It is defined as a chronic illness, lasting longer than 3 months, in which a patient has high levels of EBV DNA in their blood in the absence of a weak immune system [26].
Symptoms of the disease mirror many of those of an acute infection, such as fever and swollen lymph glands. More serious complications such as an enlarged spleen and low red blood cell, white blood cell, and platelet counts occur frequently in these patients [26].
Most of those with a chronic infection will test negative for EBNA antibodies, or they may have very low levels [27].
Over time, their immune systems may fail, and if left untreated, they will develop opportunistic infections, multiorgan failure, and cancer [26].
The only effective treatment for chronic active EBV is bone marrow transplantation [26].
Abnormal Results: What Now?
The most important thing is to work with your doctor to get an accurate diagnosis and to monitor your condition.
There are currently no vaccines to prevent mono nor drugs approved for treating mono. The symptoms usually just run their course.
Antiviral drugs have been suggested for treating mono; however, a recent review found no proof of their effectiveness, and concluded that the studies in support of the treatment were of low quality [28].
However, there are steps you can take to manage the symptoms of mono, including [29]:
- Getting enough rest
- Avoiding intense exercise
- Drinking plenty of fluids and consuming enough food
- Taking Tylenol and NSAIDs (aspirin is not recommended for those with mono) to address fever and pain – remember to discuss your medication with your doctor
- Gargling with salt water and using pain-relieving throat lozenges
After your symptoms resolve, the virus will remain in a dormant state in your body, usually without causing any further symptoms. However, you will still test positive for some EBV-specific antibodies, and the virus may reactivate under certain conditions.
If you suspect that you have a reactivated EBV infection, check out this post for more strategies to get back to full health.
Takeaway
The EBV test is used to diagnose infectious mononucleosis. It detects the presence of antibodies that the body makes to fight the infection. The monospot test is convenient, fast, and cheap, but less accurate.
The EBV-specific antibody test is the gold standard, but results take longer, and it’s more expensive.
While there are no treatment options if you have mono, symptoms can be managed by resting, drinking enough fluids, and avoiding exercise.
