Ever since patients first started reporting long hauls of COVID-19, many of their lingering symptoms, such as fatigue and brain fog, have been compared to chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME).
New research suggests that's no coincidence. In some cases, both chronic illnesses might have similar roots. A recent study among 185 COVID-19 patients in the United States has found the majority of 'long haulers' the researchers tested were positive for Epstein-Barr virus (EBV) reactivation.
Recent research has found that a subset of CFS/ME patients show signs of EBV reactivation, and now, it seems that a potentially large percentage of people with long COVID do as well.
EBV is one of the most common viral infections out there. The vast majority of people around the world contract the virus at some point in their lives, and after the acute infection phase, an inactive version of the virus sticks around in the body for a lifetime.
Sometimes, EBV can reactivate and cause flu-like symptoms, such as during periods of psychological or physiological stress.
Like, say, a global pandemic.
"We ran Epstein-Barr virus serological tests on COVID-19 patients at least 90 days after testing positive for SARS-CoV-2 infection, comparing EBV reactivation rates of those with long COVID symptoms to those who never experienced long COVID symptoms," explains biologist Jeffrey Gold of World Organization.
"We found over 73 percent of COVID-19 patients who were experiencing long COVID symptoms were also positive for EBV reactivation."
What's more, many of the reported symptoms are very similar to those that arise from EBV reactivation, including extreme fatigue, frequent skin rashes and Raynaud's phenomenon, which causes decreased blood flow to the fingers and toes. In the past year, long haulers have even taken to calling their swollen and red extremities 'COVID toes'.
Although the size of the sample studied here is very small, the results suggest many long COVID symptoms may not actually arise from SARS-CoV-2 itself, but from EBV reactivation, potentially triggered by the widespread inflammation of COVID-19.
Among all 185 randomly selected COVID-19 patients, researchers found nearly a third experienced unshakeable symptoms that lasted for months, sometimes even more than a year.
In a random sample of the study subjects, nearly 67 percent of long haulers showed antibodies for EBV reactivation in their bloodwork. At the same time, only 10 percent of patients with no long-term symptoms tested positive for EBV reactivation.
The researchers also recruited a second group of people whose COVID-19 diagnoses had been received 21-90 days before. Even in these short-term subjects, the ratio of EBV reactivation was similar.
"We found similar rates of EBV reactivation in those who had long COVID symptoms for months, as in those with long COVID symptoms that began just weeks after testing positive for COVID-19," says molecular microbiologist David Hurley from the University of Georgia.
"This indicated to us that EBV reactivation likely occurs simultaneously or soon after COVID-19 infection."
Earlier this year in Wuhan, China, researchers also found evidence that EBV reactivation might be associated with COVID-19 in its earliest stages. Within two weeks of COVID-19 infection, more than 50 percent of all 67 COVID-19 patients in the study showed signs of EBV reactivation. And this co-infection of EBV and SARS-CoV-2 was associated with more severe symptoms.
As early as last year, in fact, another small ICU study in Europe showed that positive EBV DNA was observed in roughly 87 percent of the 104 COVID-19 patients examined.
If EBV really does reactivate in such a large percentage of COVID-19 patients, it's worth understanding their relationship further.
The researchers behind this latest study think that it could even be worth testing new COVID patients for EBV antibodies. If these patients show signs of EBV reactivation, they could possibly receive further medical treatment to protect them against the risk of developing severe or long forms of COVID-19.
Of course, not all long haulers will show EBV reactivation, and some recovered COVID-19 patients can show evidence of EBV reactivation without suffering from any lingering symptoms. That said, a test like this could help identify where health risks are greatest and help us plan accordingly.
While there is currently no drug that is licensed to specifically treat EBV reactivation, there are medications that can help reduce the viral load, giving the immune system a break.
A recent study from China, for instance, found that administering the antiviral drug, ganciclovir, can decrease the risk of severe illness developing among COVID-19 patients.
A similar drug, known as valganciclovir, also appears to reduce some of the symptoms of CFS/ME, at least among patients who show antibodies for EBV, but research in this area is still in its infancy.
How EBV is connected to certain cases of CFS/ME is still hotly debated. There are those who think the virus can directly trigger this chronic illness, while others think the illness comes first before causing inflammation that can reactivate EBV infections.
While diseases and autoimmune conditions other than COVID-19 are known to trigger EBV reactivation, the authors say SARS-CoV-2 appears particularly good at poking this viral beast.
"While EBV reactivation may not be responsible for all cases of recurring fatigue or brain fog after recovering from COVID-19, evidence indicates that it likely plays a role in many or even most cases," the researchers explain.
The study was published in Pathogens.