Physiological overlap between ME/CFS and long COVID

Whilst long COVID is a heterogenous condition (with over 200 associated symptoms), there is a certain proportion of individuals within this group who meet ME/CFS criteria such as the Canadian Consensus Criteria (CCC). As many people report that an infectious illness preceded the development of their ME/CFS symptoms, it may not come as a surprise that some individuals note symptoms of ME/CFS following a SARS-CoV-2 (COVID-19) infection.
Adding to a wider body of research, Dr Katie Peppercorn and colleagues conducted a pilot study exploring whether long COVID and ME/CFS (pre-COVID pandemic) are similar on a physiological level. The researchers found similarities in immune system activity, involving an array of proteins and molecular pathways, between the two conditions.

What did the study do?

The aim of the pilot study was to ‘identify specific areas of cellular physiology that were still dysfunctional’ in individuals with long COVID one year on from their initial SARS-CoV-2 infection. The hypothesis was that there would be similar molecular pathways affected which would contribute towards explaining the ‘closely overlapping symptoms and pathophysiology of both long COVID and ME/CFS.’
The researchers analysed proteins in immune cells – known as peripheral blood mononuclear cells (PBMCs) – of six individuals with long COVID and five healthy controls matched for age and sex. The results of the analysis were compared to a previous study with an ME/CFS cohort (diagnosed according to the CCC).

What did the study find?

Analysis of over 3000 proteins identified 162 proteins that were differentially regulated (different in level/activity) in individuals with long COVID compared to healthy controls. 37 of these proteins were related to immune system activity and 21 were related to mitochondrial function – major areas of interest in ME/CFS research.
There was some overlap in differentially regulated proteins in the participants with long COVID compared with the ME/CFS cohort. However, it should be noted that not all differences were statistically significant.


According to the researchers the results indicated that the immune system activity of participants with long COVID, one year after onset of illness, was ‘dramatically different’ from that of healthy controls. They mentioned that this reflects a ‘chronic dysfunctional state that had not been restored from the expected transient/inflammatory response mounted to cope with the original infection from the SARS-CoV-2’.

As per a recent news article – ‘Lead author Emeritus Professor Warren Tate says the research – the first comparative molecular study of the immune cell proteins of both conditions [long COVID and ME/CFS] – “strongly affirms” the link between the two.’ Hence, the study implies therapeutic targeting of immune/inflammatory pathways as treatment as an area worth exploring.

The small sample size, as is typical for a pilot study, does affect the generalisability of the findings. Additionally, there was a discrepancy inn the average duration of illness  – one year for individuals with long COVID versus 16 years for the ME/CFS cohort. The researchers state that it is possible that differences could reflect the variance in timepoints since the onset of the conditions in the respective cohorts. Hopefully, these limitations are accounted for in future studies, further advancing our knowledge of both long COVID and ME/CFS.

Read about estimating ME/CFS prevalence in individuals with long COVID:

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