Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and CFS... Maes et al

[Andy]

Full title: Increased galanin-galanin receptor 1 signaling, inflammation, and insulin resistance are associated with affective symptoms and chronic fatigue syndrome due to long COVID

Abstract

Background
Patients with Long COVID (LC) often experience neuropsychiatric symptoms such as depression, anxiety, and chronic fatigue syndrome (CFS), collectively referred to as the physio-affective phenome of LC. Activated immune-inflammatory pathways and insulin resistance significantly contribute to the physio-affective phenome associated with LC.

Methods
In a cohort of 90 individuals, categorized into those with and without LC, we evaluated, 3-6 months following acute SARS-CoV-2 infection, the correlations between the Hamilton Depression (HAMD), Hamilton Anxiety (HAMA), and Fibro-Fatigue (FF) Rating Scale scores, and serum C-reactive protein (CRP), prostaglandin E2 (PGE2), galanin-galanin receptor 1 (GAL-GALR1) signaling, insulin resistance, insulin-like growth factor (IGF-1), plasminogen activator inhibitor-1 (PAI1), S100B and neuron-specific enolase (NSE).

Results
HAMD, HAMA, FF scores, CRP, PGE2, GAL-GALR1 signaling, insulin resistance, PAI1, NSE, and S100B are all higher in people with LC compared to those without LC. The HAMD/HAMA/FF scores were significantly correlated with PGE, CRP, GAL, GALR1, insulin resistance, and PAI1 levels, and a composite score based on peak body temperature (PBT) – oxygen saturation (SpO2) (PBT/SpO2 index) during the acute infectious phase. A combination of biomarkers explained a large part of the variance in CFS and affective scores (33.6%-42.0%), with GAL-GALR1 signaling, PGE2, and CRP being the top 3 most important biomarkers. The inclusion of the PBT/SpO2 index increased the prediction (55.3%-67.1%). The PBT/SpO2 index predicted the increases in GAL-GALR1 signaling.

Conclusion
These results indicate that the CFS and affective symptoms that are linked to LC are the consequence of metabolic aberrations, activated immune-inflammatory pathways, and the severity of inflammation during the acute phase of SARS-CoV-2 infection.

Open access

 

[Utsikt]

Patients with Long COVID (LC) often experience neuropsychiatric symptoms such as depression, anxiety, and chronic fatigue syndrome (CFS), collectively referred to as the physio-affective phenome of LC.

Are they saying that ME/CFS is a mood disorder?

 

[Hutan]

• Wasim Talib Mahdi Al Masoodi,
• Sami Waheed Radhi,
• Habiba Khdair Abdalsada,
• Mengqi Niu,
• Hussein Kadhem Al-Hakeim,
• Michael Maes

Maes, the senior author, has a long history of producing papers that are not quite solid.
Most of the others are from Iraq, which is not to say they can't produce a useful paper, but they probably have not had a lot of contact with a range of more established ME/CFS researchers and so may have been quite influenced by Maes.

Niu has an affiliation with an odd collection of departments in Chengdu, China including 'Key Laboratory of Psychosomatic Medicine':

Sichuan Provincial Center for Mental Health, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China, Key Laboratory of Psychosomatic Medicine, Chinese Academy of Medical Sciences, Chengdu, China

So, there could be something in the core findings and it's worth taking a look, but some of the interpretation is likely to be a bit off.

 

[Hutan]

Are they saying that ME/CFS is a mood disorder?

We've seen the fatigue of ME/CFS described as a 'neuropsychiatric' symptom before and I try not to be offended by it. I find it a term that is quite hard to get to grips with. I think it is supposed to be used for some sensations arising from disordered brain function. So there are two possible problems with the term when applied to ME/CFS

1. it's assuming something about the cause of the sensations that people with ME/CFS feel that might not be true
i.e. the depression and anxiety may have nothing to do with disordered brain function and be a normal and pretty rational response to the circumstances e.g. worried about how to pay the bills, grieving the losses; the fatigue may be arising from things happening outside of the brain, as may be the pain.

2. it may be assuming that the disordered brain can become ordered if only the person had a bit of will power and was a bit smarter about how they live

 

[Utsikt]

We've seen the fatigue of ME/CFS be described as a 'neuropsychiatric' symptom before and I try not to be offended by it. I find it a term that is quite hard to get to grips with.

I read it as them saying that ME/CFS = fatigue, and that this fatigue is a mood disorder. But I might be completely mistaken?

 

[Hutan]

I don't think you are mistaken. But, I wouldn't be too bothered about the words around the numbers, they probably are based on all sorts of odd ideas. I feel sorry for the people with Long Covid in Karbala, Iraq, and the rest of us too who have to put up with unfounded assumptions, but there's so much around already that this paper probably doesn't make that much difference.

As usual, there is a circularity in the link between emotional symptoms and Long Covid. Having emotional symptoms after Covid-19 qualifies someone as having Long Covid: presumably anxiety and depression would count for the two required symptoms. It should come as no surprise then that the Long Covid group has higher average ratings on measures of anxiety and depression.

60 Long Covid patients; 30 controls who had had Covid. Criteria for Long Covid seems as good as most.

The patients were identified based on the WHO post-COVID (long COVID) case definitions [47], which include the following: (a) individuals with a history of proven SARS-CoV-2 infection; (b) symptoms that persisted past the acute stage of illness or manifested during recovery from acute COVID-19 infection; (c) symptoms that lasted at least 2 months and are present 3–4 months after the onset of COVID- 19; (d) patients who have no less than two symptoms that make it challenging to do every- day undertakings, for example, fatigue, headaches, trouble speaking, chest pain, a persistent cough, loss of taste or smell, emotional symptoms, mental hindrance, or fever [47]. None of these criteria were met by the thirty controls.

The Long covid group had had, on average, a worse acute illness: longer duration, higher peak temperature, lower minimum blood oxygen saturation. The mean lowest blood oxygen saturation in the Long Covid group was 80%, way less than the 93% of the controls. That's interesting, but I don't know how relevant it is to people with the ME/CFS pattern of symptoms.


So, the Long covid group is likely to have been, as is usual, a mixture of people, including people recovering from a moderate to severe Covid-19 illness and/or people with an ME/CFS symptom pattern and/or people who have lost their sense of taste or smell or mental sharpness and feel sad about that.


Mean time from acute illness to study inclusion was 16 to 17 months.
The sex ratios were not similar between the two groups (2/3 male in the controls and around 1/2 male in the LC group)
They say they adjusted results for age, sex and BMI.

Here are the results:

Glucose, insulin, HOMA2IR, CRP, PAI1, PGE2, NSE, GAL, GALR1, and S100B were significantly increased
in long COVID patients in comparison with the controls. There was a significant decrease in HOMA2%S in long COVID compared with controls, whereas IGF-1 was not significantly different between both groups.

HOMA2IR is a measure of insulin resistance and HOMA2%S is a measure of insulin sensitivity.

 

[Hutan]

We've got to get researchers to stratify their "Long Covid" samples into more descriptive subsets. This lumping is just hopeless.

 

[Utsikt]

We've got to get researchers to stratify their "Long Covid" samples into more descriptive subsets. This lumping is just hopeless.

Agreed!