Leaving aside this nonsense …
The COVID-19 pandemic, as a massive social stressor, may have triggered changes in social behavior, which could manifest as part of the broader symptomatology of long COVID. The possible linkage between the genes associated with abnormal social behavior and long COVID fatigue, may reflect the broader biopsychosocial impact of long COVID, influencing both the brain's functional connectivity and the patient's emotional and social response to the condition.
… I'm struggling to follow their overall logic and consistency.
Abstract says said:
Compared to healthy controls, long COVID patients exhibited significantly higher fatigue scores and shifted the brain into a less segregated state at both 1-month and 3-month post-infection. During the recovery of fatigue severity, there was no significant difference of segregation/integration. A positive correlation between network integration and fatigue was observed at 1-month, shifting to a negative correlation by 3-months.
That seems to be saying more integration and less segregation correlates with more fatigue, at 1 month. But then at 3 months the brain changes persist ("no significant difference of segregation/integration") but the fatigue is decreasing/improving ("recovery")?
In the body of the manuscript, they say —
Normal brain functions depend on both the relatively independent processing within specialized systems (segregation) and the global cooperation between different systems (integration).
Neuroimaging studies have identified a characteristic pattern of functional connectivity (FC) changes in COVID-19 patients, e.g., decreased connectivity within higher order cognitive networks, including the default mode network (DMN), salience network (SN), frontoparietal network (FPN) and somatomotor network (SMN).
fatigue is a prominent symptom of long COVID, and it is thought to be linked to the dynamics of integration and segregation [17]
[17] is
Fatigue and resting-state functional brain networks in breast cancer patients treated with chemotherapy (2021, Breast Cancer Research and Treatment)
In this study, 34 long COVID patients recovered from an initial mild SARS-CoV-2 infection underwent neuropsychological measurements and MRI scans at 1-month and 3-month post infection. healthy controls followed the same protocol as the 1-month post-infection group simultaneously.
long COVID patients at 1month post-infection exhibited significantly higher scores on the MFI-20 total score (p < 0.001 […] Between 1-month and 3month post-infection, the reductions in the MFI-20 total score and all subscales were observed, but only the decrease in MFI-20 total score and general fatigue was statistically significant (p = 0.032, p = 0.014, Bonferroni-corrected), reflecting a potential recovery of MFI at three months. […] when directly comparing the control and 3-month post-infection, the MFI20 total score and most subscales in 3-month post-infection are still significantly higher than those for HC (MFI-20 total score: p < 0.001
Compared to HCs, 1-month post-infection patients showed a significant increase in network integration, and a decrease in segregation […] consistently observed in network integration and segregation across nearly all networks […] At the regional level, most of regions has the increased integration and decreased segregation at 1-month post-infection relative to HC.
There was no significant difference of segregation/integration between the 1-month and 3-month post-infection groups in the whole-brain, system and regional scales, even the recovery of MFI. But compared to the HCs, 3-month post-infection patients had insignificant change of integration (-0.485±0.046, p = 0.918) and significantly decreased segregation (-0.405±0.048, p < 0.001).
So consistently they're reporting increased integration and decreased segregation. But the integration seems to have normalised by 3 months (as shown in their figure).
While the MFI had a recovery across MFI-20 (total score and all subdimensions (general fatigue, physical fatigue, mental fatigue, reduced activity, and reduced motivation)) from 1-month to 3-month, the brain network didn’t show a significant change of integration and segregation, such that the correlation between brain networks and MFI-20 may be alternated from 1-month to 3-month.
But for 3-month post-infection group, the correlation trends were opposite. MFI-20 total score and nearly all the subdimensions of MFI-20 were significantly negatively correlated with network integration and positively correlated with segregation
So this is the reversal of correlation between 1 and 3 months. There's no change in brain findings, but fatigue scores have now reduced. (Doesn't that mean there's no correlation and fatigue is independent of brain network integration/segregation?)
In the discussion —
the brain networks of long COVID patients tend to be more integrated and less segregated, with more pronounced changes at 1-month. Third, the correlation between brain network segregation and fatigue severity shifted from negative at 1month to positive at 3-month post-infection. […] Our results further confirm that during the acute phase, long COVID patients suffered a highly integrated and less segregated brain
aligns with the theory that COVID-19 stress induces a dynamic reallocation of resources between brain networks to maintain a hypervigilant state, promoting threat detection and survival
Then they say —
At 3-month post-infection, global- and network-level integration was no longer significantly different from that of healthy controls and the reduction in segregation had partially diminished, indicating a partial recovery of brain network function in tandem with improvements in fatigue symptoms over time. Nevertheless, a decrease in segregation remained evident
So integration at 3-months was now the same as HCs and segregation was less reduced but not normal — all while fatigue scores were decreasing.
Then they reference chronic fatigue syndrome, claiming replicative findings, but the reporting seems backwards.
In patients with chronic fatigue syndrome, fatigue is negatively correlated with integration [32, 33], which are consistent with our results, implying long COVID fatigue aligning closely with typical pathological changes associated with chronic fatigue conditions. More specifically, our results indicate that long COVID fatigue is linked to increased segregation and decreased integration, particularly in DAN and VN, and is most evident in reduced motivation.
Haven't they been highlighting increased
integration and decreased
segregation through all this?
[32] is The importance of glutamate in the neuro-endocrinological functions in multiple sclerosis, related to fatigue (2018, Rev Neurol,
PubMed)
[33] is
Acute stress promotes brain network integration and reduces state transition variability (2022, Proceedings of the National Academy of Sciences) which doesn't even mention the word fatigue.
Then they conclude this section with —
This shift from physical fatigue to reduced motivation may be driven by altered brain segregation in VN and DAN. Since visual processing plays a critical role in selective attention and the VN can influence mental health by facilitating communication between higher-order cognitive networks, the FPN and the DMN. Our findings emphasize the importance of the visual system and attention network in shaping long COVID fatigue perception.
<shrug emoji>
