Reactivation of Herpes virus in Long Covid and ME CFS

Research Review: Reactivation of human herpesviruses and their role in ME/CFS and Long Covid

By Dr Katrina Pears 20 January 2023 

To read the full article including details of the 3 research papers reviewed click the button below

Audio Commentary by Dr Katrina Pears


In this research summary we look at the role of reactivated human herpesviruses (HHV) in ME/CFS and Long Covid. This is because a number of recent studies have implied that HHV’s could be involved in disease pathology causing and perpetuating symptoms. And because this might lead to effective treatments and diagnostic tests. 

HHVs have the ability to trick their host’s immune system. This means it doesn’t completely eradicate them and the virus can remain dormant (latent) only to be reactivated at a later stage. Latency helps the virus to survive and following a trigger, to spread. Once reactivated they can cause temporary symptoms or persistent disease. Latent viruses are triggered in multiple ways including by other infections, a weakened immune system, stress, trauma and by hormonal changes. 

The onset of ME/CFS often follows a viral infection and the most common is Epstein Barr Virus (HHV4). Reactivated HHVs have been linked to ME/CFS and a number of other diseases, including Alzheimer’s and Multiple Sclerosis. We know that Covid-19 (a Coronavirus) is the trigger for Long Covid, but this virus might also cause dormant HHVs to become active and contribute to symptoms and chronic ill-health. 


There are over 100 different herpesviruses, but only 8 are commonly found to infect humans. These include HHV4, HHV6, HHV7, and HHV8. 

The most common HHV is Epstein-Barr Virus (EBV) (or HHV4). It is found all over the world and has infected almost the entire population. Most people experience a mild infection during childhood, but infection in teenage years can develop into glandular fever, or mononucleosis, and is also known as ‘the kissing disease’. 

Another well-known and relatively common infection is Chickenpox (HHV3), caused by the Varicella-Zoster Virus. This is often an acute infection that is nearly always caught in childhood, with reactivation potentially causing Shingles in later life.  

Cytomegalovirus (CMV) (HHV5) causes widespread infection, which is usually harmless, unless contracted during pregnancy where it can potentially harm babies, or by people with a weakened immune system where it can be fatal. In the USA nearly 1 in 3 children have been infected by CMV by the age of 5. 


  • Fluctuating symptoms in ME/CFS could be a result of repeated HHV reactivation, and abnormal immune responses following a triggering event such as infection with another virus. 
  • Saliva is a good to use when studying HHV’s due it being key to transmission, with the salivary gland being a particularly permissive site for HHV replication. But results also suggest the active virus may hide in inaccessible locations requiring post-mortem access. 
  • Results may vary depending on the HHV studied.  

Existing research has shown some variation in results, especially as it examined different HHVs using different samples (blood, saliva, or post-mortem tissue). But we hope they are used as the basis for more research, as larger cohorts and more conclusive results could lead to the development of new and effective treatments that might boost antiviral immune responses and lead to immunological tests that improve the effectiveness of ME/CFS (and Long Covid) diagnosis.  

New Research 

Research is currently underway at Brunel University in London into the role of reactivated HHV-6B infection in ME/CFS and Long Covid. It is led by 2 members of the UK ME/CFS Biobank team: Professor Jackie Cliff at Brunel and Dr Eliana Lacerda at the London School of Hygiene and Tropical Medicine: 

“We hypothesise that the characteristic persistent remitting and relapsing nature of the ME/CFS syndrome in many individuals is the result of repeated HHV-6B reactivation, due to abnormal immune responses in susceptible people following an initial triggering event such as infection with another virus.” 

It will focus on participants recording their symptom severity to determine whether changes in HHV-6B concentration in saliva occurs before or after changes in ME/CFS symptoms. This will allow scientists to determine if HHV-6B causes the symptom changes or if these occur after the disease gets worse. 

The study will also investigate immune cell function, specifically in cytotoxic T cells, including responses to stimulation, and at the impact of HHV-6B on other immune cells. A pilot study from this team has already demonstrated that the concentration of DNA from HHV-6B was higher in saliva from people with ME/CFS, and that the concentration correlated with the severity of symptoms (Lee et al., 2021).  

Dr Katrina Pears,
Research Correspondent.
The ME Association.

Dr Katrina Pears - MEA Research Correspondent
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