Long Covid and its association with Epstein Barr Virus, EBV, reactivation
August 9th, 2021
This is a very important topic for clinicians and parents to understand so we are going to look at it a little more deeply.
Long COVID or what appears to be a post infectious inflammatory issue may now be a consequence of another infection. What are the symptoms of long COVID and when do they occur? From the CDC: Some people
are experiencing a range of new or ongoing symptoms that can last weeks or months after first being infected with the virus that causes COVID-19. Unlike some of the other types of post-COVID conditions that only tend to occur in people who have had severe illness, these symptoms can happen to anyone who has had COVID-19, even if the illness was mild, or if they had no initial symptoms. Symptoms can even begin weeks after the infection. People commonly report experiencing different combinations of the following symptoms:
• Difficulty breathing or shortness of breath
• Tiredness or fatigue
• Symptoms that get worse after physical or mental activities
• Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
• Chest or stomach pain
• Fast-beating or pounding heart (also known as heart palpitations)
• Joint or muscle pain
• Pins-and-needles feeling
• Sleep problems
• Dizziness on standing (lightheadedness)
• Mood changes
• Change in smell or taste
• Changes in period cycles
In the journal Pathogens, Dr. Gold notes that a 6.7x increase in EBV reactivation in long COVID patients based on antibody titer measurements. We do not know if EBV is driving the long COVID so much as a reflection of the inadequate immune T helper cell activity that should be present in immune solvent individuals attempting to clear a viral pathogen. It has been shown in different studies over the past year that individuals with poor T cell activity, TH1, Natural killer cells, NK and poorly polarized macrophages, MAC2, are at increased risk for a worse COVID morbidity and/or mortality outcome. (Gold et. al. 2021)
The science: My friend, Dr. Sam Yanuck, writes: We could imagine the patient’s Th1 system becoming suppressed in several ways, leading to expansion of EBV burdens, even in a patient who had managed to eradicate SARS-CoV-2 from their system. 1) GI or respiratory involvement of COVID-19 would be expected to increase epithelial inflammatory activation, driving Th2-promoting cytokines, at the expense of Th1, 2) stress chemistry from the biological and psychological stresses of COVID-19 infection would be expected to induce apoptosis, programmed cell death, of Th1 cells and NK cells, and 3) inflammatory effects from COVID-19 would be expected to upregulate MDSC’s, myeloid derived suppressor cells, driving down Th1 response. In this third option, we would expect to see high TGFβ. There are likely plenty of other ways to get to low Th1, given the moving parts involved in SARS-CoV-2 infection.
Let me break this paragraph down. What Dr. Yanuck is saying is that our immune system's natural immune polarization to fight different types of infections can be compromised by the invading SARS2 infection or other antecedent lifestyle based risk factors which we will look at below. The virus itself is triggering immune dysregulation by causing significant mental and physical stresses coupled to inflammation that drives an abnormal immune polarity driving down viral suppression ability by reducing the function of TH1 cells, NK cells and M1 macrophage activity. The precursor risk tied to the infection response can drive this immune viral interface problem leading to a reactivation of herpes viral infections further chronically taxing the system leading to what looks like long COVID or chronic fatigue.
If a patient is suffering from COVID but survives, it is highly possible and likely that the immune system was so tasked fighting the SARS2 virus that the ability to tackle the indolent EBV virus is compromised allowing for a resurgence and a chronic fatigue fighting state to ensue. This is hypothetical only but plausible based on the fact that SARS2 does suppress immune viral killing capacity and herpes viruses sit dormant in many of us waiting for a time of stress to reactivate from dormancy. EBV is known to infect and become indolent in over 90% of Americans. The measurement of a biomarker is NOT conclusion of cause and effect. However, there are patients that appear to have long COVID and feel well when they are on an antiviral medicine that theoretically contains EBV's growth. More time and data will answer these questions, yet, I am aligned with the physiological premise that our stress biochemistry, nutritional biochemistry and microbiome are somehow driving a dysregulated immune activation and response leading to a chronic brain fog and fatigue state that we are calling long covid.
If this data pans out to be real and associated with the symptoms as seen in these patients, then we need to spend time working to optimize T Helper type 1 cell, natural killer cell and macrophage type 1 activity. The question remains now for explanation, how do we do that?
In the basic science literature, we see that hyperglycemia impairs the immune surveillance and killing mechanisms allowing viral expansion and subsequent problems. We know that diabetic patients have a compromised pathogen killing capacity. (Giese et. al. 2021) (Berbudi et. al. 2020) High volumes of saturated fat are known to trigger immune dysregulation via multiple pathways including pattern recognition receptors, T helper cells and inflammasomes. (Veldhoen et. al. 2012) However, there are many genetic and epigenetic variables that make these dietary immune generalizations only exactly that. There has been much study of mental, physical and environmental stressors affecting immune viral function.
It is my opinion that the human immune system was and is set up to respond to pathogens robustly based on exposure and normal existence. For thousands of years we were exposed to varied food availability and type. Thus, it would make complete sense to me that the immune system would work well in many types of dietary patterns as well as periods of starvation or short periods of excess. I think that chronic starvation and chronic caloric excess are the breakpoints for immune dysregulation. The basic science literature is reasonable to draw these conclusions especially as it pertains to diabetes mellitus and in my mind insulin resistance, IR, as well. Remember that IR is a downstream effect of chronic exposure to excess fats followed by excess sugars.
This modern human shift in macronutrient intake has stressed the metabolic systems and therefore the immunological systems to the point of poor pathogen recognition, surveillance and killing capacity. I believe that we have solid epidemiological data to support this contention as well. Over 96% of COVID related deaths were in individuals with deranged metabolism from poor dietary choices leading to four disease: diabetes, coronary heart disease, hypertension and obesity.
If your child or anyone that you know is suffering from Long Covid, focus on the basic lifestyle principles that impair viral surveillance and killing. That will allow for a more robust immune response to the herpes viruses that may be underlying the symptoms of brain fog, fatigue and autonomic instability. The reversal of this problem appears to be a long process as the immune system does not change on a dime despite the rapidity of cellular turnover. Discuss the use of antiviral medicines and other targeted supplements to enhance immune activity with your provider if Long Covid is a problem for you.
Mental stress is a major driver of immune dysfunction. Focus heavily on stress reduction methods as discussed in the past coupled to therapy and conscious positive verbalization about self. Make sure that sleep is a cherished healing event that is allowed to happen on schedule nightly.
Finally, I think that time restricted feeding events or Ketogenic diets may play a role here in the right candidate that is not too cachectic or struggling overall with food body image issues.
Very important to search for clues as to why so many people are suffering from prolonged post COVID symptoms. This is just the beginning,
CDC Long Covid
Giese Frontiers in Immunology
Berbudi Curr Diabetes Reviews
Veldhoen Nature Reviews Immunology