Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19 infection

Abstract:

Objective and design: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is a major symptom of the long-COVID syndrome. The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19 infection.

Subjects and methods: We tested this hypothesis by analysing pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19 positive and COVID-19 negative participants were categorized based on antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale.

Results: COVID-19 positive participants exhibited mild symptoms of infection. Chronic fatigue was a prevalent symptom among this population and was significantly higher in the COVID-19 positive participants than COVID-19 negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in COVID-19 positive and COVID-19 negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in COVID-19 negative, but not COVID-19 positive
individuals. Raised BMI was associated with chronic fatigue in COVID-19 positive participants.

Conclusions: We found evidence that pre-existing increased levels of IL-6 provide the ground for chronic fatigue symptoms but there was no specific link seen with mild COVID-19 status. Elevated BMI increased the risk of chronic fatigue in mild COVID-19 infection consistent with previous reports.

Source: B Freidin, M., Borsini, A., Pariante, C., & MK Williams, F. (2023). Long-COVID fatigue is not predicted by prepandemic plasma IL-6 levels in mild COVID-19 infection. Inflammation Research. https://kclpure.kcl.ac.uk/portal/files/201594849/Freidin_et_al._2023.pdf (Full text)

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