Can You Get Mono More Than Once?

Most people will only experience mononucleosis (mono) once, but in rare cases, the infection can come back a second time. Mono is caused by the Epstein-Barr virus (EBV), which is a type of herpes virus. It’s such a common infection that it's estimated that roughly 90% of the American population has become infected with EBV by the time they reach the age of 35.

For many people, symptoms of mono are mild or non-existent. Common symptoms include extreme fatigue, sore throat, fever, and body aches. Many other conditions share these symptoms, so it's important to see your healthcare provider for an accurate diagnosis.

a sick woman sleeping

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Mononucleosis Recurrence

Mono can recur because the body does not get rid of the virus even after the symptoms of the infection disappear. Once a person becomes infected with mono, EBV stays in their body for life by remaining in tissues and immune cells. While the body still carries the virus, it is dormant.

Also referred to as a latent infection, when a virus is dormant, it ceases to fight or replicate to take over cells. Essentially, it goes to sleep and no longer affects cells or causes symptoms. During this time, the body continues to create antibodies to fight the virus, which leads to immunity if the virus ever becomes active again.

In many cases, reactivation of EBV is not associated with new symptoms. The infection can again be spread to other people.

Although it is rare, mono can remain active for a long period of time and develop into a chronic active Epstein-Barr virus (CAEBV) infection.

Risk Factors for Recurrence

People who are especially at risk for a recurrence of mono are those with a compromised immune system, those who have undergone organ transplant surgery, and those who are pregnant. People with weakened immune systems are most at risk for recurrence because of how the virus affects immune cells—specifically, natural killer cells and T cells. If a person has defects in these two types of immune cells, fighting off the virus becomes significantly more difficult.

Other Possible Causes of Symptoms

Symptoms of mono are similar to those of many other illnesses, so it can be easy to confuse a mono infection with another condition, such as:

  • Strep throat: This bacterial infection causes a sore throat, a symptom that is common among those who have mono. If left untreated, a case of strep throat can lead to kidney inflammation or rheumatic fever.
  • The flu: The symptoms that occur in both mono and the flu include fever, sore throat, body aches, headaches, and fatigue.
  • Cytomegalovirus (CMV) infection: Similar to mono, once a person becomes infected with CMV, it stays in their body for life. In healthy people, CMV rarely causes any symptoms, so most people are unaware they have the virus at all. When symptoms do occur, they can mimic mono. The symptoms of CMV are virtually identical to those that occur in mono and include fatigue, sore throat, fever, and swollen glands. In some cases, an infection with CMV can cause mono.
  • Hepatitis A: This is a type of liver infection caused by the hepatitis virus. Like mono, it is highly contagious, but it is spread in different ways. The symptoms that can occur in both mono and hepatitis A include an enlarged liver, fever, and fatigue.
  • Rubella: Rubella is a contagious disease caused by the rubella virus. For many who contract the illness, symptoms are mild. It is thought that anywhere from 20% to 50% of people with rubella are asymptomatic. The symptoms of rubella that overlap with those of mono include fever, sore throat, swollen or enlarged lymph nodes, and a rash.
  • Myalgic encephalomyelitis (ME): Otherwise known as chronic fatigue syndrome, ME is another condition that is commonly mistaken for mono. This is because extreme fatigue is a symptom in both illnesses. Other ME symptoms that occur in a mono infection include swollen lymph nodes and a sore throat.

When to Call Your Healthcare Provider

Experiencing the symptoms of mono can be difficult to deal with. This is especially true if the virus has reactivated. If you are ill with the symptoms of mono and have previously had the infection, it’s best to call your healthcare provider right away to get a proper diagnosis. Since it is highly unlikely that the infection occurs twice, it’s likely that your symptoms are caused by something else.

If you have a recurrent infection, getting enough rest, fluids, and symptom relief is the best way to cope with the symptoms. Keeping your healthcare provider up-to-date on the progression of the illness will help them provide you with the best medical advice.

Frequently Asked Questions

  • Can you get mono twice?

    No. Once you have had mono, the virus lays dormant in your body after symptoms go away. For most people, the virus only causes symptoms once. However, sometimes a latent infection can cause a recurrence of mono symptoms. 

    While it is unclear exactly why this happens, it is believed physical or emotional stress may be the culprit. During a recurrence, you may be able to spread the virus to others. 

  • Are you immune to mono after having it?

    Yes. The Epstein-Barr virus that causes mononucleosis stays in your body after an infection. You cannot catch mono twice. If you have already had mono, you do not have to worry about catching it again if you are re-exposed.

  • Do you always test positive for mono after having it?

    It depends on the test. Laboratory tests for Epstein-Barr virus (EBV) antibodies can remain positive for decades. In-office tests that use a drop of blood to check for EBV antibodies can remain positive for up to a year. However, rapid mononucleosis tests are no longer recommended for diagnosing mono due to a high rate of false negatives and positives.

12 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Angelica Bottaro
Angelica Bottaro is a professional freelance writer with over 5 years of experience. She has been educated in both psychology and journalism, and her dual education has given her the research and writing skills needed to deliver sound and engaging content in the health space.