Discovery of molecular signature of long-term psychiatric sequelae in COVID-19 through proteome profiling of dried blood spots, 2025, Baik et al.

[SNT Gatchaman]

Discovery of molecular signature of long-term psychiatric sequelae in COVID-19 through proteome profiling of dried blood spots

Spoiler: Authors

Baik, Myungjae; Yeom, Jeonghun; Lee, Sang Min; Jeong, Hwangkyo; Lee, Ah Rah; Seo, Seungyoon; Choi, Sung Moon; Jo, Yeonwoo; Park, Hye Yoon; Kim, Eun Young; Paik, Jong-Woo

Neuropsychiatric sequelae represent a significant aspect of post-acute sequelae of SARS-CoV-2 (PASC, or long COVID), posing considerable public health challenges. This study identified molecular signatures associated with PASC in individuals with psychiatric morbidities via dried blood spot proteomic analysis.

We evaluated 51 COVID-19 survivors ≥ 60 days post-infection, categorizing them into three groups: those with new-onset psychiatric disorders (n = 16, psychiatric PASC), those with persistent symptoms but no psychiatric disorders (n = 18, general PASC), and those symptomatically recovered (n = 17, recovered). Liquid chromatography-mass spectrometry analysis identified 1604 proteins. Differentially expressed proteins underwent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.

Protein panels, including isoform 1 of fibronectin, sorbitol dehydrogenase, cytosolic acyl coenzyme A thioester hydrolase, and apolipoprotein A-II, differentiated psychiatric PASC from recovered individuals with an area under the curve (AUC) of 0.865 (95% CI: 0.658–1). Filamin A and vacuolar protein sorting-associated protein VTA1 homolog distinguished psychiatric PASC from general PASC at an AUC of 0.831 (95% CI: 0.6–1). Decision tree analysis revealed that alpha-synuclein, pyruvate kinase PKM, and sorbitol dehydrogenase effectively distinguished the three groups with 82% classification accuracy.

These findings suggest that alterations in immune, glucose, and lipid metabolism pathways, along with neuroinflammation and neurodegeneration, contribute to the psychiatric PASC phenotype and highlight potential biomarkers for psychiatric disorders during the long-term COVID-19 clinical course.

Web | PDF | Nature Translational Psychiatry | Open Access

 

[boolybooly]

This paper speaks to me as I am having a lot of problems with symptoms related to diabetes 2 like insulin resistance after suspected COVID-19 reinfection corresponding to Nimbus variant symptoms. So imho its a real phenomenon, possibly related to the way COVID-19 spike messes with ACE2 receptor and upsets RAS and insulin regulation.

At a first reading it is a bit scary because of the psychological terminology and the way, as we approach Halloween, the dried blood spot DBS idea conjours images of blood spattered day-room walls as if some fictional drama (like Terminator or 12 Monkeys or many a Zombie movie), though this appears to be a proper clinical process, merely reporting facts and is not pursuing, horror of horrors, a BPS agenda.

It does however have an angle, as it is promoting proteomics in economically impactful healthcare methodology and one of the lead contributors works for a proteomics company called Prometabio. The other works at the Department of Psychiatry, Kyung Hee University Hospital, Seoul. Which implies South Korea is treating PASC brain fog etc as psychiatric conditions, which technically they are and I am hopeful this does not mean they dismiss these symptoms as amenable to CBT and GET like BPS proponents did with ME. The paper appears to take steps towards investigating the metabolic causes behind the psychiatric conditions.

prometabio

프로메타바이오

www.prometabio.com

I dont have a problem with promoting hard science and if proteomics could provide a metric for some PASC conditions that would be welcome. What I would be cautious about with this paper would be the small cohort size. I think this needs to be replicated on a larger scale by independent researchers.

 

[rvallee]

Psychiatric disorders were clinically diagnosed using the Mini-International Neuropsychiatric Interview (version 7) by a trained psychiatrist.

Not much detail beyond that.

Participants in the psychiatric PASC group had significantly higher levels of depressive symptoms, anxiety, and post-traumatic stress symptoms and lower levels of functional social support than those in the other groups. Individuals in the psychiatric and general PASC groups reported elevated levels of sleep disturbance and fatigue and lower quality of life than those in the recovered group.

It really all depends on what the definition of 'psychiatric' is, which after years of reading straight from the sources has less meaning than I started with. Something mostly about impacting function to the point of being behaviorally noticeable but has an unknown cause, is about the best interpretation I can have.

So this should mostly be used as a study of Long Covid where there is a tiny difference on questionnaires that ask overlapping questions with the common symptoms of LC:

The mean (SD) total number of PASC symptoms (range, 0–33) was 10.4 (6.2) in the psychiatric PASC and 8.5 (5.4) in the general PASC, and 1.1 (1.5) in the recovered group.

Otherwise this looks pretty solid, but it seems to be much more about post-infectious chronic illness than anything to do with psychiatry.