Predictors of fatigue progression in long COVID among young people, 2025, Brodwall

[Dolphin]

https://www.sciencedirect.com/science/article/pii/S2666354625000407

Brain, Behavior, & Immunity - Health
Volume 45, May 2025, 100982
Predictors of fatigue progression in long COVID among young people

Elias Myrstad Brodwall Lise Lund Berven a,c a,b,* , Joel Selvakumar , Erin Cvejic d a,b , Lise Beier Havdal , Vegard Bruun Bratholm Wyller a b c
a
Dept. of Pediatrics and Adolescent Health, Akershus University Hospital, Lørenskog, Norway
b
Institute of Clinical Medicine, University of Oslo, Oslo, Norway
c
Dept. of Clinical Molecular Biology (EpiGen), University of Oslo and Akershus University Hospital, Lørenskog, Norway
d
The University of Sydney, School of Public Health, Faculty of Medicine and Health, The University of Sydney, Australia
e
Dept. of Pediatric Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
Received 28 November 2024, Revised 19 February 2025, Accepted 23 March 2025, Available online 24 March 2025, Version of Record 26 March 2025.


https://doi.org/10.1016/j.bbih.2025.100982Get rights and content
Under a Creative Commons license
Open access

Highlights

• •
  Post-COVID fatigue in young people gradually declines the first year post-infection.
• •
  A range of variables are associated with fatigue progression.
• •
  Non-European ethnicity, immune, and sympathetic activity predict fatigue progression.
• •
  Treatment gives a fatigue reduction.

Abstract

Long COVID, or post-COVID-19 condition (PCC), has emerged as a significant health concern, with fatigue being the most prevalent persistent symptom among young people.

However, research on predictors of fatigue progression in young populations is limited.

This study aimed to investigate factors during acute SARS-CoV-2 infection that could predict fatigue progression between six and 12 months post-infection in a cohort of young people with chronic fatigue following COVID-19.

Data from the Long-Term Effects of COVID-19 in Adolescents (LoTECA) project were analyzed.

A total of 93 participants (mean age 18.5 years, 84 % female) with chronic fatigue at six months, completed the 12-month follow-up.

Multivariate analyses identified non-European ethnicity, higher interferon gamma (IFN-γ) levels, and lower RR-interval (higher resting heart rate) during acute infection as significant predictors of fatigue progression from six to 12 months.

These three factors explained 21 % of the variance in the fatigue score, highlighting the importance of ethnicity, immune response, and autonomic function in the trajectory of long COVID fatigue.

Early identification and targeted interventions, particularly for ethnic minorities and those with specific immune or autonomic markers during acute infection, may be helpful in reducing long-term fatigue.

Further research is needed to explore treatment strategies for affected young populations.
Keywords
Post-infective fatigue syndrome (PIFS)
Post-COVID condition (PCC)
Long COVID
Chronic fatigue
Adolescents
SARS-CoV-2
Fatigue trajectory
Fatigue risk factors

 

[SNT Gatchaman]

A number of reasonable points.

In this study, participants are already fatigued, and we are focusing on risk factors for the subsequent changes from that point onward.

The association between compliance with the WHO’s PCC criteria at six months and subsequent change in fatigue was non-significant. In contrast, a diagnosis of PIFS based on the Fukuda definition at the same timepoint showed a trend towards significant correlation with fatigue progression over the following six months. This further calls into question the utility of the WHO’s criteria, being too broad and unspecific, as highlighted in previous publications (Selvakumar et al., 2023).

Interestingly, though non-European ethnicity correlated with lower socioeconomic ranking in our study, the latter was not associated with fatigue progression.

Illness beliefs, influenced by accurate information from health care providers, are critical according to several studies (Burton et al., 2024; Rozenkrantz et al., 2022). If ethnicity influences access to accurate healthcare information and if illness beliefs vary across cultures, these factors may mediate the observed effects of ethnicity on health outcomes. Yet, ethnicity did not correlate with (Klepstad et al., 2002) on illness belief in our data, but rather on self-efficacy (GSE-6). Higher scores on the self-efficacy questionnaire are indicative of more social support, better mental health, and active problem-focused coping (Romppel et al., 2013). Scores on self-efficacy in the non-European group did not seem to correlate with fatigue scores however, though our sample size is too small to conclude.

Interestingly, baseline symptoms potentially linked to high sympathetic nervous activity, such as orthostatic dizziness and cold and pale hands, were also associated with fatigue progression from six to 12 months. Taken together, these results suggest a positive prognostic effect of parasympathetic over sympathetic heart rate control at rest.

Notably, our correlation analysis revealed a significant association between IFN-γ and symptoms such as pale and cold hands, which are indicative of autonomic dysfunction

In the bivariate analysis, immunoglobulin G (IgG) was associated with fatigue progression in a manner consistent with our IFN-γ findings (eSupplementary Table 2). However, IgG did not remain in the final model, possibly due to its correlation with heart rate variability

 

[SNT Gatchaman]

though non-European ethnicity correlated with lower socioeconomic ranking in our study, the latter was not associated with fatigue progression

Illness beliefs, influenced by accurate information from health care providers, are critical according to several studies. If ethnicity influences access to accurate healthcare information and if illness beliefs vary across cultures, these factors may mediate the observed effects of ethnicity on health outcomes. Yet, ethnicity did not correlate with on illness belief in our data, but rather on self-efficacy (GSE-6).

So as non-European ethnicity correlates with lower socioeconomic ranking, which influences (ie reduces) access to healthcare, we might well draw the conclusion that not being exposed to the "accurate healthcare information" is protective.

 

[Utsikt]

Multivariate analyses identified non-European ethnicity, higher interferon gamma (IFN-γ) levels, and lower RR-interval (higher resting heart rate) during acute infection as significant predictors of fatigue progression from six to 12 months.

These three factors explained 21 % of the variance in the fatigue score, highlighting the importance of ethnicity, immune response, and autonomic function in the trajectory of long COVID fatigue.

21 % for the three most significant factors does not seem very impressive to me.

 

[Andy]

"a diagnosis of PIFS based on the Fukuda definition", will be part of the continuing effort by the authors of rebranding ME/CFS as PIFS.

 

[Utsikt]

For LC: 61 out of 154 (40 %) with a CFQ score >=4 at 6 months were lost to follow up at 12 months.

For controls: 17 out of 28 (61 %) of the eligible participants at 12 months were lost to follow up.

The 61 individuals who declined the 12-month follow-up assessments were broadly similar to those who attended, including comparable CFQ scores at baseline and six months. However, they reported a higher quality of life and had a lower resting heart rate (higher RR-interval) (eSupplementary Table 1).

Yet the findings were that higher resting heart rate was correlated with fatigue.

 

[Utsikt]

Participants who received treatment for post-COVID symptoms between the six- and 12-month follow-up showed a tendency towards reduced fatigue compared to those who did not, especially the few who specified type of treatment (eSupplementary Tab. 3).

First of all, the reference is incorrect, it’s Tab. 4.

More importantly, the trend was not statistically significant. Meaning that the people that received treatments did not improve more that those that didn’t.

 

[Eleanor]

Chalder Fatigue Questionnaire. [sound of someone scrunching up paper and dropping it in the bin]

 

[rvallee]

Early identification and targeted interventions, particularly for ethnic minorities and those with specific immune or autonomic markers during acute infection, may be helpful in reducing long-term fatigue.

Yes, if you could treat the problem, you could treat the problem. Very insightful. It's so nice to dream of things, imagine if people actually did the work to develop the thing. The rest doesn't any more useful, none of this is a predictor of anything.

How is the quality of research not going up at all? It's what baffles me. It's as if mediocre failure is a comfortable blanket and no one wants to step out into the cold.