Pre-Pandemic Plasma IL-6 Levels are Positively Associated with Chronic Fatigue But Do Not Differentiate Those with COVID-19 Induced Fatigue
Abstract
Background – Fatigue is a prominent symptom in the general population and may follow infection with a number of viruses including SARS-CoV2 causing COVID-19. Persistent or chronic fatigue lasting more than 3 months following COVID-19 infection is a major symptom of so-called long-COVID syndrome. The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of post-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual before COVID-19 infection.
Methods – We tested this hypothesis by analysing pre-pandemic plasma levels of IL-6, one of the key cytokines in fatigue development, in n = 1274 community dwelling adult twins from TwinsUK. TwinsUK registry participants have been assessed longitudinally for persistent fatigue using selfcompleted questionnaire; and for COVID-19 infection by antigen and antibody testing.
Findings – Persistent fatigue was a prevalent symptom among this population but the prevalence was found to be significantly higher in the COVID-19 antibody positive- compared to antibody negative twins (17% vs 11%, respectively; p = 0.001). The qualitative nature of persistent fatigue as determined by individual question responses was similar in those having had COVID-19 and those not having infection. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in COVID-19 negative, but not positive, individuals; while raised BMI was found associated with chronic fatigue in COVID-19 positive twins.
Interpretation – This finding corroborates our hypothesis that pre-existing immune status provides the ground for chronic fatigue, but we found no evidence that this occurs specifically in COVID-19 infection.
The study (preprint): https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4188566
Abstract
Background – Fatigue is a prominent symptom in the general population and may follow infection with a number of viruses including SARS-CoV2 causing COVID-19. Persistent or chronic fatigue lasting more than 3 months following COVID-19 infection is a major symptom of so-called long-COVID syndrome. The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of post-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual before COVID-19 infection.
Methods – We tested this hypothesis by analysing pre-pandemic plasma levels of IL-6, one of the key cytokines in fatigue development, in n = 1274 community dwelling adult twins from TwinsUK. TwinsUK registry participants have been assessed longitudinally for persistent fatigue using selfcompleted questionnaire; and for COVID-19 infection by antigen and antibody testing.
Findings – Persistent fatigue was a prevalent symptom among this population but the prevalence was found to be significantly higher in the COVID-19 antibody positive- compared to antibody negative twins (17% vs 11%, respectively; p = 0.001). The qualitative nature of persistent fatigue as determined by individual question responses was similar in those having had COVID-19 and those not having infection. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in COVID-19 negative, but not positive, individuals; while raised BMI was found associated with chronic fatigue in COVID-19 positive twins.
Interpretation – This finding corroborates our hypothesis that pre-existing immune status provides the ground for chronic fatigue, but we found no evidence that this occurs specifically in COVID-19 infection.
The study (preprint): https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4188566