Correlates of fatigue in SARS-CoV-2-positive and -negative adolescents and young adults: Repeated cross-sectional analyses…, 2026, Brodwall, Wyller+

[SNT Gatchaman]

Correlates of fatigue in SARS-CoV-2-positive and -negative adolescents and young adults: Repeated cross-sectional analyses from a prospective cohort study

Spoiler: Authors

Brodwall; Selvakumar; Havdal; Sommen; Berven; Cvejic; Wyller; Pedersen

PURPOSE
To investigate cross-sectional associations between concurrent fatigue and a range of covariates in adolescents and young adults with acute SARS-CoV-2 infection and follow-up six months after infection, as well as in SARS-CoV-2-negative controls.

METHODS
A total of 404 SARS-CoV-2 -positive adolescents and young adults were studied during their infection and again six months post-infection, compared to 105 SARS-CoV-2-negative controls. In this exploratory study, cross-sectional linear regression analyses were conducted at each time point to examine associations between fatigue and a range of covariates, including biomarkers, functional tests, symptoms, and psychological traits.

RESULTS
Fatigue was significantly and strongly associated with all other symptoms (p < 0.001), poor sleep quality (p < 0.001), psychological traits and negative emotions (p < 0.001), and lower quality of life (p < 0.001), across all cohorts. During the early convalescent phase of SARS-CoV-2 infection, fatigue showed few cross-sectional associations with immunological or autonomic markers, whereas such associations were observed six months after infection. COVID-negative controls also displayed immunological associations with fatigue.

CONCLUSIONS
Fatigue was consistently linked to concurrent symptom burden, insufficient sleep, negative emotions, and reduced quality of life, irrespective of infection status or timing. The lack of immunological and autonomic associations with fatigue during the early convalescent phase of SARS-CoV-2 infection are followed by their presence at six months. Findings suggests that the pattern of correlates may differ over time. These exploratory cross-sectional findings are non-causal and cannot establish directionality but are compatible with neuroscientific models on persistent symptoms and sustained arousal.

HIGHLIGHTS
• Fatigue is strongly tied to symptom burden, sleep, mood, and life quality.

• Symptom–fatigue associations are similar in acute COVID, post-COVID, and controls.

• Acute COVID fatigue shows minimal immunologic or autonomic associations.

• Immune and autonomic correlates emerge only with prolonged post-COVID fatigue.

Web | DOI | Journal of Psychosomatic Research | Open Access

 

[Utsikt]

From the simple regression model:

Autonomic markers were associated with fatigue exclusively in the C6 cohort (Table S4). All HRV indices (RMSSD, SDNN, RR-interval, ln-transformed LF and HF power) showed significant negative associations with fatigue, indicating that higher cardiac autonomic variability and parasympathetic activity were related to lower fatigue severity, whereas reduced HRV was associated with increased fatigue.

From the multiple regression model:

In this dataset, only one instance exceeded the VIF threshold for multicollinearity: IL-9 and MIP-1β in the immunologic category of the C6 cohort demonstrated VIF above 50.

There is no mention of HRV in this section. I wonder why..

Later on they say that mothers might be causing some of the symptoms in their children:

Unexpectedly, residing with their mother and not father is associated with higher levels of fatigue in all cohorts. The exact reasons for this association remain unclear, but existing research has demonstrated that women generally report more symptoms than men, as in this current study, and that children may be predisposed to inherit symptomatology from their mothers [34], [35]. This could suggest that residing with a mother may contribute to increased symptom reporting among those in such environments. However, it is also possible that children with confounding risk factors for fatigue are prone to live with their mothers. Nonetheless, this finding emphasizes the need for a deeper understanding of how familial dynamics can influence health outcomes. This finding should be interpreted with caution, however, as residing with a mother did not remain in any final multivariate model after robustness testing.

Then they try to knock down the «tissue pathology» strawman and propose that it might be «central processing» instead:

Academically, the consistency of these broad and robust associations across cohorts may challenge prevailing models that conceptualize symptoms as directly reflecting underlying tissue pathology. Instead, these strong and consistent associations may point toward symptom generation as a function of central processing mechanisms, rather than a direct readout of tissue damage. [20], [21], [41].

Ref 21 is about hysteria. They are really trying to make a case for treating everyone with «symptoms» the same.

They left the best for last: the sustained stress response:

During the early convalescent phase (CP), no relationship was observed between autonomic measures and fatigue levels. However, a consistent association pattern appeared after six months (C6).

Specifically, a lower RMSSD in the C6 cohort indicates reduced vagal modulation and increased sympathetic activity, coherent with a lower SDNN, RR-interval, and HFAbs values. Likewise, lower LFAbs suggests an autonomic imbalance.

Summarized, the associations between fatigue and the various heart rate variability (HRV) measures six months after COVID-infection indicate a sustained stress response.

With no correlation at CP, and only one measurement at C6 at a single timepoint, I don’t understand how you can define it as «sustained». They mention in the conclusion that you can’t determine the temporal (or causal) direction, but that doesn’t stop them from trying!

And of course there is no mention about how people that have been feeling bad for a long time and probably been less active, might have different HRV data because of the inactivity.

These findings support the notion of chronically fatigued patients being in a “sustained arousal”, and are coherent with previous findings in chronic fatigued populations [16].

As a limitation, HRV parameters in this current study are derived from less reliable short-term resting ECGs, 24-h recordings may provide different results.

Unsurprisingly, there is no mention of Wyller’s own recent negative findings related to the correlation between stress and long term fatigue after EBV infection, which is the kind of measurement that might be less impacted by confounders compared to a resting state ECG!

Thread 'The association between hair cortisol levels, Epstein-Barr virus infections and chronic fatigue in adolescents, 2026, Kongsnes, Wyller et al'

Mar 7, 2026

https://www.tandfonline.com/doi/full/10.1080/10253890.2026.2638303

Research Article

The association between hair cortisol levels, Epstein-Barr virus infections and chronic fatigue in adolescents​

Berit Elise Bergem Kongsnes
,
Tarjei Tørre Asprusten
,
Vegard Bruun Bratholm Wyller
&
Maria Pedersen
Article: 2638303 | Received 20 Nov 2025, Accepted 23 Feb 2026, Published online: 02 Mar 2026

• https://doi.org/10.1080/10253890.2026.2638303

Abstract​

Chronic fatigue after Epstein-Barr virus (EBV) infection is a significant health...

• Dolphin
• cortisol ebv
• Replies: 19
• Forum: ME/CFS research

• 

There’s no correction for multiple comparisons:

Finally, this study is based on an exploratory statistical approach with many candidate variables, which entails an increased risk of overfitting, false-positive findings, and model instability. The results should therefore be interpreted with caution and regarded as hypothesis-generating.

And no mention of the memberships in OCFN etc. that have a very explicit view about the cause of fatigue and «symptoms», like they were forced to add to the COI in the recent opinion piece.

 

[rvallee]

Fatigue was significantly and strongly associated with all other symptoms

Yes, because despite decades of making this all about fatigue, it's always fatigue and other symptoms. What the hell are these people even talking about here? It's literally definitional, in ME/CFS as in LC and in most chronic illnesses. It's almost like they're showing that they never listen to a damn thing patients tell them.

I have no idea what this even has to do with anything psychosomatic, other than the very public and obvious bias of the authors, who want to argue that but always pretend like they're just finding this stuff through careful study. Who is this even for?!