Infectious Mononucleosis - Nate Pearson and the "kissing disease"

Epstein-Barr Virus micrography

Two viral particles (virions) in round capsids with a loose membrane around them

Greetings dear "azur" avian dinosaur descendants.

("azur" is an Occitan (ie, similar to Catalán) word meaning blue, coming from Arabic, who took the name from the persan rock lapis lazuli. What is known in English as the French Riviera is named Côte d'Azur (ie Blue coast))

It has recently emerged that Nate Pearson is currently suffering from mononucleosis. That disease, which does have a weird non-specific name, usually lasts a couple of weeks, but symptoms may sometimes affect an individual for months. Let's hope that's not the case for Nate.

The name of the disease simply is the reflection of an accumulation of mononuclear leukocytes (meaning monocytes, macrophages and lymphocytes) in swelled ganglia. This is caused by an infection, most commonly (90%) a virus from the herpes virus family such as Epstein-Barr Virus (EBV, or human gammaherpesvirus 4). Rarer causes involve another human herpesvirus, cytomegalovirus (CMV, human betaherpesvirus 5).

These viruses are very common, but in contrast to popular thinking, they are not highly infectious. This means that while almost everyone gets exposed to them, only a portion of the population actually gets infected. The nickname "kissing disease" comes from the saliva-specific transmission, which is best exchanged by "French kissing", but also through drinking and eating utensil sharing and toothbrushes sharing. Furthermore, infected children do not develop the typical symptoms experienced by their elders; infectious mononucleosis is thus a teenager/young adult disease right at the same time as other new experiences.

Now, it's not my purpose to speculate in anyway on Nate Pearson's personal life.

EBV and CMV are double-stranded DNA viruses, meaning they are very different from SARS-CoV-2 and influenza viruses, but instead carry their genome much like living organisms do. They are part of the human herpes virus family, which also includes herpes simplex virus 1 and 2 (the virus causing human herpes disease), varicella zoster virus (causing varicella (chicken pox) and shingles (zoster)) and the aforementioned EBV and CMV. Almost all human adults have been infected by at least one of these and keep a latent form in their cells.

Sidenote: shingles may be debilitating disease, highly painful, which exemplifies different immunization strategies. In North America, the advent of the varicella vaccine led to widespread immunization of children; the vaccine is also widely distributed to seniors, with a goal to reduce the viral circulation. In Europe, however, the strategy is different. Instead of immunizing children, in whom the infection is benign in almost every case, the authorities let the virus run rampant, immunizing only the few adults who never got infected. The idea is that the more often a person gets infected, the better the person's immune response is to a reactivation of the virus in later life. In essence, multiple expositions from childhood provides a better (and almost free) protection against shingles in later life, with the vaccine plugging the holes. How much does this situation affect EBV immunization, I don't know.

EBV is also known to cause multiple sorts of cancers (around 200k annually) and has recently been implicated (in a retrospective longitudinal study) in the development of multiple sclerosis (MS). It infects B lymphocytes (the cells producing antibodies) and epithelial cells (the lining of cells facing the exterior, such as the skin, gastric track, pulmonary air vessels and genitals). The B cell infection explains all the bone-marrow-linked cancers EBV can cause; the epithelial cell infection explains stomach cancer and nasopharyngeal cancer. The latter also explains the typical sore throat of mononucleosis.

Latency is restricted to B lymphocytes. After infection and the development of an immune response, the EBV shuts down most of its gene expression, keeping only those necessary to transform its B cell host into an "immortal" reproducing cell in the bone marrow. In fact, it co-opts the B lymphocyte's mechanisms to activate and reproduce after it recognizes an antigen; EBV does it without antigen recognition. How and why the virus can reactivate itself remains unclear. It also seems that EBV-infected B lymphocytes can enter the brain and contribute to multiple sclerosis.

CMV is a different beast. It is mostly harmless in immunocompetent individuals, but may be deadly in HIV and other immunocompromised patients and newborns. It is among the absolute experts at evading the immune system, remaining latent until an opening (such as an immune suppressing treatment) lets it cause disease. It's also implied in many cancers. It's one of the few pathogens transmitted from the mother to the infant (along with Rubella, toxoplasmosis and herpes simplex) and, thus, a leading case of neonatal malformations. CMV positive bone-marrow transplants and blood transfusion are not proscribed, but care must be applied to make sure the recipient is matching the donor's CMV status. Older readers might recall tennis player Justine Henin's struggle with CMV in 2004.

Without much information, it's impossible to know what is the cause of Nate Pearson's mononucleosis. it is most likely EBV; let's hope he does not suffer from other complications. If he was indeed free from EBV infection before, his chances of developing multiple sclerosis have, possibly*, increased 30-fold. It can be more difficult for athletes to recover fully, since they push their bodies to a much higher level that most of us. The cycling superstar Mark Cavendish basically lost two full years of performance after a EBV infection, which also led to a depression. He then bounced back in a spectacular fashion last Summer, winning 4 Tour de France stages.

There is no treatment for mononucleosis or EBV infection, except time and rest. Antiviral drugs would target DNA synthesis, a mechanism of action that tends to create very unpleasant side effects. There is currently no vaccine for EBV.

So, let's be patient with Nate. He needs to rest and recover for as long as necessary. It's crucial not to rush him back. There are things more important than baseball, even for an athlete, and while EBV is most commonly mild in symptoms, it is no joke.

Here is a very recent article in The Atlantic about EBV.

*The study is impressive. The US DoD routinely tests its members for markers such as HIV; those serum samples are conserved. Among the 10 million subjects from 1993 to 2013, there were enough EBV-negative samples (around 5%, or 200 000) to make a statistically significant group of them. They then followed the rates of EBV-infection and MS over 20 years. The DoD screens its members every two years, and there were 62 million leftover samples which let the investigators follow EBV-seropositivity evolution in time. But not all of them were included in the study: 801 individuals who developed MS were found and then matched with twice the number (1566) of matched random controls (for age, etc). Only 1 MS case was EBV-seronegative at any point. In contrast, "only" around 60% of the MS-free individuals EBV-seronegative individuals got infected. The 32-fold increase figure uses the EBV-seronegative individuals as a reference point; the individuals already EBV-seropositive also had an increased risk (26-fold) of MS. Since most of us already carry EBV, we're almost all at risk of increased MS. But it is likely that a recent infection in a naive host of Pearson's age increases the risk of MS a lot more than in the general population. His own personal chances to develop MS have thus increased a lot, but his baseline risk was lower.

Editor's Note: This is a FanPost written by a reader and member of Bluebird Banter. It was not commissioned by the editors and is not necessarily reflective of the opinions of Bluebird Banter or SB Nation.