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Long-term Effects Of Mononucleosis Chronic Fatigue Syndrome

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What Is Chronic Fatigue Syndrome?
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In December of 2012, I came down with what at first looked like a bad case of mononucleosis. I felt tired and had a sore throat, a cough, and a slight fever. At the time, I was twenty-six and working as an adjunct English professor at a small college in Westchester, New York. It was Christmas break, so I thought that I would sleep it off and feel better by the New Year. But over the next few months my symptoms grew to include muscle pain, migraines, and occasional vertigo. The cough went away but the tiredness got worse, and by the summer I was spending half my time resting in bed. I was used to playing pickup basketball several times a week after work, but now a few pushups left me exhausted. I couldnt figure out what was happening. One afternoon, as an experiment, I went for a run near my apartment, in uptown Hoboken. I clipped my iPod Shuffle to my mesh shorts and jogged past Italian delis with dry-cured sausages in their windows and along a pier that hugged the Hudson. It felt amazing. But the next day, while grading papers with a few other teachers, suddenly, I became dizzy and weak. I left the office without explanation, and, for the next several days, I barely left my bedroom.

A previous version of this story incorrectly described cytokines and misstated the location of a clinic dispensing Ampligen.

Clinical Symptoms And Presentation

POTS can occur in a variety of different clinical situations. It commonly occurs in young females and is associated with lightheadedness, palpitations, fatigue, confusion, chest pain, and headaches. Only rarely does syncope occur.

POTS is characterized as being primary or secondary. The primary form is a partial dysautonomic form, which may be related to a postviral syndrome or could be merely related to aging. There is also a hyperadrenergic form. Diabetes, a paraneoplastic syndrome, and joint hypermobility syndromes have been described as possible etiologies in secondary forms. There are potential poorly defined psychiatric problems, including anxiety neuroses, that are present in individuals with POTS.

Secondary POTS is due to peripheral autonomic denervation and can occur with diabetes, amyloidosis, sarcoidosis, lupus, heavy metals, alcoholism, chemotherapy, and Sjögrens syndrome. It can occur in pure autonomic failure or multiple system atrophy and paraneoplastic syndromes. In the latter, it may be due to autoantibodies to acetylcholine receptors of the ganglia similar to postviral POTS.

The differential diagnoses include dehydration, hyperthyroidism, drugs, supplements such as guarana, caffeine, IST, supraventricular tachycardia, pheochromocytoma, anemia, pulmonary emboli, and panic disorder.

Dianne J Newham, Kerry R Mills, in, 2003

Norwegian Researchers Studied Adolescents Who Developed Chronic Fatigue Syndrome And Chronic Fatigue After Having Mononucleosis

Chronic fatigue syndrome affects thousands of people in Norway.

Little is understood about the cause of the disease, but research has shown that it can be triggered by infections. Many people develop ME/CFS following a bout of mononucleosis sometimes called mono or the kissing disease which is a viral infection caused by the Epstein-Barr virus.

But not everyone who gets mono ends up with chronic fatigue syndrome. What separates those who get ME/CFS from those who dont? Understanding these differences could give us hints about which mechanisms are behind ME/CFS.

The results of a Norwegian study that explored this very question have now been published.

Different interpretations

The results show some small differences in the immune system between people who regain their health and those who develop ME/CFS or other chronic fatigue after mono, but not enough to explain the dramatic disparity in symptoms.

Professor Vegard Bruun Bratholm Wyller led the study and believes the results support the hypothesis that ME/CFS is due to a hypersensitivity in the brain. This leads to signals from the outside world being over-interpreted because the nervous system is on continuous high alert.

Professor and paediatrician Kristian Sommerfelt, on the other hand, believes that the results only show that the participants with a lot of symptoms after their bout with mono more often develop chronic fatigue, and in some cases chronic fatigue syndrome.

Almost half developed CF or ME/CFS

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Reactivated Ebv Can Become Chronic

Chronic, reactivated EBV is an amped-up version of mononucleosis, with a range of symptoms, including:

  • Profound fatigue
  • Irritated mucous membranes
  • Swollen lymph nodes

Reactivated EBV can also cause a host of debilitating neurological symptoms. The symptoms can wax and wane for years, and severe cases can involve liver dysfunction, immune suppression, and even anemia. The most plausible explanation for why chronic, reactivated EBV is so severe and unrelenting is that its not just EBV at play.

For instance, people often carry other herpesviruses in addition to EBV. The list includes herpes simplex types 1 and 2 , varicella-zoster virus , cytomegalovirus , HHV-6 types a and b, HHV-7, and HHV-8. Though theyre all related, each of these viruses infects the body in a different way therefore, they cause slightly different symptom profiles. In important ways, theyre all remarkably prevalent and share a common characteristic:

The Long Term Effectsof Mononucleosis In Chronic Fatigue Syndrome

Effects Of Mononucleosis In Chronic Fatigue Syndrome?

What makes mononucleosis infection different from other viral infections is the fact that even after the virus subsides, the patients still feel lingering post-viral symptoms. These symptoms include weakness and fatigue. Typically, a viral infection may last for one to two weeks, after which the patient return s back to their usual perky selves. But with the mono infection, patients stay almost bedridden and weak even after the viral infection subsides. Fatigue and body weakness linger for more extended periods, even lasting for months. This scenario is the reason why people ask about the term effects of mononucleosis in chronic fatigue syndrome.

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More Severe Mononucleosis In College Students Increases The Risk Of Severe Chronic Fatigue Syndrome 6 Months Later

Ann & Robert H. Lurie Children’s Hospital of Chicago
To assess risk factors for chronic fatigue syndrome after mononucleosis, researchers developed and validated a scale for rating the severity of mononucleosis. In a study with 126 college students, they found that participants with a higher mononucleosis severity score had over three times the risk of meeting two or more sets of diagnostic criteria for chronic fatigue syndrome after six months.

One to five percent of college students develop infectious mononucleosis each year, and about 10 percent are diagnosed six months later with chronic fatigue syndrome — a complex condition involving severe fatigue coupled with disabling cognitive and musculoskeletal symptoms. To assess risk factors for chronic fatigue syndrome after mononucleosis, researchers developed and validated a scale for rating the severity of mononucleosis. In a study with 126 college students, they found that participants with a higher mononucleosis severity score had over three times the risk of meeting two or more sets of diagnostic criteria for chronic fatigue syndrome after six months, as well as almost twice the chance of being prescribed steroids and an increased risk of being hospitalized during the acute illness. Their findings were published in the Journal of Pediatrics.

Multiple studies have identified two treatments that may be effective for chronic fatigue syndrome — graded exercise therapy and cognitive behavioral therapy.

Early Complications To Infectious Mononucleosis


As mentioned, parenchymal injury of the liver tissue is common with about 75% of patients exhibiting a two to three fold increase in ALAT during the acute phase of infection with levels returning to normal after about three weeks . Cholestatic liver disease and chronic hepatitis due to EBV are rare complications, but have been described in the literature . The hepatic changes are therefore usually transient and self-limiting, but cases of liver failure with fatal outcomes – even in immunocompetent patients – have been reported which is why it is advisable to order liver tests upon diagnosis and during monitoring of patients with more severe IM.

Splenic rupture

Airway compromise

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Preventing The Spread Of Infection

There is no need to be isolated from others if you have glandular fever as most people will already be immune to the Epstein-Barr virus .

You can return to work, college or school as soon as you feel well enough. There is little risk of spreading the infection to others as long as you follow commonsense precautions while you are ill, such as not kissing other people or sharing utensils.

It is also important to thoroughly clean anything that may have been contaminated by saliva until you have recovered.

Does Bad ‘mono’ Predict Chronic Fatigue Syndrome

CHRONIC FATIGUE SYNDROME, Causes, Signs and Symptoms, Diagnosis and Treatment.

HealthDay Reporter

TUESDAY, April 2, 2019 — As if having the exhausting “kissing disease” — also known as mononucleosis, or “mono” — isn’t bad enough, about 1 in 10 people with this infection will develop chronic fatigue syndrome in six months, researchers report.

To better predict which people with mono might end up with debilitating chronic fatigue syndrome, investigators at Lurie Children’s Hospital of Chicago developed a new scale to rate how severe a mononucleosis infection is. They then tested it in 126 college students diagnosed with mono.

“We looked at what factors correlated with bad outcomes and then tried to validate these measures,” said Dr. Ben Katz, an attending pediatric infectious diseases specialist.

People with the most severe mononucleosis infections based on the new scale were more than three times as likely to meet the diagnostic criteria for chronic fatigue syndrome, Katz explained.

And three factors in particular often showed up in people with more severe mono. These included:

  • Being unable to leave home when symptoms were worst.
  • Experiencing digestive symptoms, such as nausea and vomiting.

Chronic fatigue syndrome is also called myalgic encephalomyelitis/chronic fatigue syndrome . The CDC says it causes extreme fatigue, sleep problems, thinking and memory issues, dizziness and pain. Symptoms can get worse after exercise. The exact cause is unknown, and it’s difficult to diagnose, the CDC noted.

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The Journal of Pediatrics

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How The Condition Progresses

Most symptoms of glandular fever will usually resolve within two or three weeks. Your throat will normally feel most sore for three to five days after symptoms start before gradually improving, and your fever will usually last 10 to 14 days.

Fatigue is the most persistent symptom and often lasts a few weeks, although some people may feel persistently fatigued for several months after the other symptoms have passed.

Causes Of Glandular Fever

Glandular fever is caused by the Epstein-Barr virus . EBV is most often spread through the saliva of someone who carries the infection.

For example, it can be spread through:

  • kissing glandular fever is sometimes referred to as the “kissing disease”
  • sharing food and drinks
  • exposure to coughs and sneezes

Small children may be infected by chewing toys that have been contaminated with the virus.

When you come into contact with infected saliva, the virus can infect the cells on the lining of your throat.

The infection is then passed into your white blood cells before spreading through the lymphatic system.

This is a series of glands found throughout your body that allows many of the cells that your immune system needs to travel around the body.

After the infection has passed, people develop lifelong immunity to the virus and most won’t develop symptoms again.

Many people are first exposed to EBV during childhood, when the infection causes few symptoms and often goes unrecognised before it eventually passes.

Young adults may be most at risk of glandular fever because they might not have been exposed to the virus when they were younger, and the infection tends to produce more severe symptoms when you’re older.

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Genetic Predisposition To Ebv Infection

The diversity of human leukocyte antigen molecules results from selective pressure during co-evolution with pathogens . A characteristic of HLA diversity is the long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species . In humans, there are 13 allelic lineages of DRB1 and, according to the phylogenetic relationship between the different DRB genes of primates described by Bontrop et al, the DRB1*04, *03 and *02 lineages are the oldest, with the DRB1*04 lineage being the most ancestral . Since EBV is the only human-adapted member of the genus Lymphocryptovirus, transferred to a hominid ancestor , it could be hypothesized that immune evasion mechanisms of the EBV have more effectively evolved among older allelic lineages of DRB1. Such an hypothesis could help explaining why individuals with haplotypes DR2-DQ6, DR3-DQ2 or DR4-DQ8 are less resistant to EBV infection and are at greater risk of developing EBV-related disorders .

Studies Relating To Infectious Mononucleosis And Me/cfs

Chronic Fatigue Syndrome Is a Real Disease
  • “Epstein-barr | Mononucleosis | About Mono | CDC”. Centers for Disease Control and Prevention. January 23, 2019. Retrieved April 8, 2019.
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  • Katz, Ben Z. Reuter, Caroline Lupovitch, Yair Gleason, Kristen McClellan, Damani Cotler, Joseph Jason, Leonard A. . “A Validated Scale for Assessing the Severity of Acute Infectious Mononucleosis”. The Journal of Pediatrics. 209: 130â133. doi:10.1016/j.jpeds.2019.01.035. ISSN 1097-6833. PMID 30853204.
  • âLennon, P. Crotty, M. Fenton, J. E. . “Infectious mononucleosis”. BMJ. 350 : 6. doi:10.1136/bmj.h1825. ISSN 1756-1833.
  • Jason, Leonard A Katz, Ben Z. Shiraishi, Yukiko Mears, Cynthia J. Im, Young Taylor, Renee R. , “Predictors of post-infectious chronic fatigue syndrome in adolescents”, Health Psychology and Behavioral Medicine, 2 : 41-51, doi:10.1080/21642850.2013.869176
  • âHickie, Ian Davenport, Tracey Wakefield, Denis Vollmer-Conna, Ute Cameron, Barbara Vernon, Suzanne D Reeves, William C Lloyd, Andrew . “Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study”. BMJ. 333 : 575â. doi:10.1136/ PMC 1569956. PMID 16950834.
  • âKatz, Ben Z. Shiraishi, Yukiko Mears, Cynthia J. Binns, Helen J. Taylor, Renee . “Chronic fatigue syndrome after infectious mononucleosis in adolescents”. Pediatrics. 124 : 189â193. doi:10.1542/peds.2008-1879. ISSN 1098-4275. PMID 19564299.
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    When Fatigue Doesn’t Improve

    For most people, the symptoms of fatigue associated with mono will gradually resolve over a period of two weeks to a few months. In a minority of people, though, fatigue may still be present six months after the initial infection. In those cases, further evaluation may be necessary.

    If fatigue persists beyond six months, your healthcare provider may start to consider a diagnosis of chronic fatigue syndrome, as EBV is theorized to be a possible cause of this disease. Though the relationship isn’t fully understood, it may represent long-standing impacts of the initial infection.

    It may also be important to look at sleep disorders that can cause sleepiness and fatigue, including obstructive sleep apnea and insomnia. These common conditions often contribute to unrestful sleep. Because they require different treatment, they shouldn’t be overlooked as having a possible role in ongoing symptoms.

    Depending on your specific symptoms, your healthcare provider may also test you for anemia and thyroid dysfunction. Depression and anxiety are also common causes of fatigue.

    Mononucleosis Doctor Discussion Guide

    Get our printable guide for your next healthcare provider’s appointment to help you ask the right questions.

    Trigger For Chronic Fatigue Syndrome

    A minority of infectious mononucleosis patients develop postviral fatigue syndrome and meet the criteria for chronic fatigue syndrome . Research studies cite figures from 7% to 13% of healthy people who contract infectious mononucleosis will have the illness progress into chronic fatigue syndrome . In a 2013 study by Jason and Katz, thirteen percent of adolescents met the criteria for CFS 6 months following infectious mononucleosis the figure was 7% at 12 months and 4% at 24 months. A year later, Jason and Katz looked at numerous medical, demographic, and psychological factors in an effort to find predictors of which infectious mononucleosis patients would develop chronic fatigue syndrome. They found the best predictor was the illness severity of the case of infectious mononucleosis.

    In 2019, Katz et al. found that severity of mononucleosis predicted risk of CFS six months post-infection.

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    Predictors For Developing Severe Myalgic Encephalomyelitis/chronic Fatigue Syndrome Following Infectious Mononucleosis

    Leonard A Jason1*, Joseph Cotler1, Mohammed F Islam1, Jacob Furst2, Ben Z Katz3

    2The College of Computing and Digital Media, DePaul University, Chicago, IL 60614, USA. Email: Jacob Furst: [email protected]


    Background: About 10% of individuals who contract infectious mononucleosis have symptoms 6 months later that meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome . Our study for the first time examined whether it is possible to predict who will develop ME/CFS following IM.

    Methods: We have reported on a prospectively recruited cohort of 4,501 college students, of which 238 developed IM. Those who developed IM were followed-up at six months to determine whether they recovered or met criteria for ME/CFS. The present study focuses on 48 students who after six months had a diagnosis of ME/CFS, and a matched control group of 58 students who had no further symptoms after their IM. All of these 106 students had data at baseline , when experiencing IM, and 6 months following IM. Of those who did not recover from IM, there were two groups: 30 were classified as ME/CFS and 18 were classified as severe ME/CFS. We measured the results of 7 questionnaires, physical examination findings, the severity of mononucleosis and cytokine analyses at baseline and at the time of IM. We examined predictors of those who developed ME/CFS and severe ME/CFS following IM.

    Why Do Viral Infections Make Us Fatigued

    Chronic Fatigue Syndrome possible long-term effect of COVID-19, experts say

    You know that feeling of being unable to get out of bed when youre sicktoo tired to sleep, too tired even to read, and you just want to lay there? That is the type of fatigue we are talking about here.

    But why does fatigue happen when fighting off certain pathogens?

    Doctors used to say a fever caused the fatigue, but more recent research shows that is likely incorrect. Instead, it is neuroinflammation inflammation in the central nervous system causing fatigue when you have a virus. This doesnt mean the virus is in your brain, but rather the inflammatory cytokines, such as IL-1 and interferon, are acting on the central nervous system. The brain then suppresses activity throughout the body.

    An interesting animal study showed that sickness behavior and cognitive dysfunction go together with viral illnesses. One key to the behavioral changes is the blood-brain barrier interferon receptor, which when activated by interferon releases a cytokine into the brain.

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