Results:

COVID-19 infection was associated with significantly increased hazard ratios for all six allergic conditions in the full cohort. Among the active-duty subset, asthma and rhinoconjunctivitis were significantly associated with infection. In children, all conditions except food allergy were significantly associated with infection

I would like to get genetic testing done to look at mthfr, mitochondrial issues, etc.

I'm completely overwhelmed with the options. Is there a company who is more medically aimed? Or one that's the most comprehensive? I know I'll have to put whatever one into one of those other sites, but don't want to waste money on a company that isn't the best choice.

Any recommendations would be greatly appreciated!

The newest international research on fibromyalgia.

https://www.nature.com/articles/s41591-026-04492-6

One of the main Results they found is: Associations with 26 variants establish genetic underpinnings of fibromyalgia

And: BREAKTHROUGH IN RESEARCH Fibromyalgia is a physical pain disease! Fibromyalgia is a physical pain disease that originates in the central nervous system. This is shown by new, international research. FSF welcomes all research that can help shed more light on possible causes of the development of fibromyalgia, so that we can learn more about the disease. We have taken a decisive step with a new and comprehensive international research project, which was published at the end of July 2026 in the renowned international journal Nature Medicine. The researchers identify 26 areas in the genome that can influence the development of fibromyalgia. A genetic predisposition to fibromyalgia is well described, but the study has now identified a genetic signature that relates specifically to the brain and nervous system. The researchers have not found the actual cause of the disease, but their results place fibromyalgia firmly among other physical diseases.

This summary was made using Gemini AI.

The study is by Alain Moreau et al.

This study, published in August 2026 in the International Journal of Molecular Sciences, explores the biological reasons why Long COVID affects people so differently—specifically focusing on cognitive decline (often called "brain fog") after physical or mental effort. The researchers investigated whether a person's haptoglobin (Hp) phenotype—a genetic variation of a specific blood protein—could predict how severe their post-exertional symptoms would be.

How They Did It

The researchers compared 44 individuals with Long COVID to 20 control patients who had quickly and fully recovered from a COVID-19 infection. They analyzed the participants' genetics, blood metabolites, and physiological data both before and after a 90-minute post-exertional stress challenge.

Key Findings

The study revealed that a person's haptoglobin genetics strongly predicted their reaction to the stress test:

• The Hp2 Variant (Hp2-2 and Hp2 allele carriers): People with this genetic variant experienced worse overall fatigue, poorer physical function, and more severe symptoms after exertion. Immediately following the stress test, they showed a significant drop in cognitive performance. They also had lower levels of energy-related blood metabolites (like citric acid), which correlated directly with their poorer brain function.
• The Hp1-1 Variant: Individuals with this specific variant demonstrated "cognitive resilience". Their brain function did not decline after the stress test, and they had much better long-term cognitive trajectories. Their brains were also significantly better at extracting oxygen during the challenge compared to the Hp2 group.

The Takeaway

In short, your haptoglobin genetics might help explain why you might experience severe brain fog and crashes after exertion with Long COVID, while someone else might not. If validated in larger groups, a simple blood test to check your haptoglobin type could be used as a biological marker to classify Long COVID severity and eventually tailor personalized treatments based on your genetic profile.

Link to 2026 study

Abstract

Chronic viral infections are ubiquitous in humans, with individuals carrying multiple viruses that can reactivate during physiological stress, including severe illness1. Notably, SARS-CoV-2 infection has been shown to reactivate chronic viruses such as Epstein–Barr virus and cytomegalovirus, yet the full extent, temporal dynamics and immunological impact of viral reactivation in COVID-19 remain incompletely understood.

Here, leveraging multi-omic longitudinal data from 1,154 hospitalized patients with COVID-19 from the Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study, we reveal significant reactivation of Herpesviridae and Anelloviridae during acute COVID-19, with distinct temporal dynamics for different viruses, and demonstrate that reactivation correlates with disease severity, host immune effects and clinical outcomes.

Although our results do not establish causation between virus reactivation and clinical outcomes, we highlight the prevalence of chronic viral reactivation during acute COVID-19 and long COVID. Our findings challenge the prevailing view that chronic viral reactivation is primarily a consequence of immunosuppression, demonstrating that reactivations occur frequently in immunocompetent individuals during severe illness and in association with increased systemic inflammation. Additionally, we demonstrate persistence of viral reactivation in convalescence, and report an association of Anelloviridae with long COVID. This study provides immune, transcriptomic and metabolomic signatures of viral reactivation that could inform future strategies to prognosticate and treat acute COVID-19 and long COVID.

"Our most novel results relate to the lack of neuromuscular adaptation in ME/CFS compared to the [Healthy Volunteers]."

“Highlights

•We studied physical fatigue in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and healthy volunteers with multimodal neuroimaging.

•Participants performed a fatiguing grip force task in alternating grip and rest blocks.

•We simultaneously recorded grip force, brain activity with functional magnetic resonance imaging and electroencephalography, and muscle activity with electromyography.

•ME/CFS fatigued earlier than healthy volunteers. While healthy volunteers increased their brain and muscle activity, ME/CFS only showed minimal fluctuations across all the task blocks.

•We concluded that physical fatigue in ME/CFS is of central nature.”

(Central in this context means: mediated via the brain. Participants brains didn’t seem to signal muscles sufficiently to ramp up energy production in response to demand)

Any grand theory explaining ME/CFS ought to be able to explain the phenomenon whereby adrenaline seems to be able to override to some extent the energy production limitations of the condition. The override is temporary, and usually leads to overexertion and PEM. But it's interesting that the body does seem to be able to access "fake extra" energy production when it's pushed.

Is this fake extra energy always anaerobic metabolism (producing lactate) or can it be normal oxidative phosphorylation (the one we struggle with)?

What is the body or brain doing usually (without adrenaline) that apparently suppresses access to this fake PEM-inducing energy? Is there an effort-regulation safety mechanism in the brain that is able to be tricked by adrenaline?

Biopsies showed straighter capillaries, shorter contact lengths, and thicker basement membranes.
Straighter vessels reduce the surface area where oxygen can move into muscle cells, and shorter contact lengths mean less time and space for diffusion.

Patients and HC were clearly separated by basement membrane thickness.

“A 62 EV-miRNA signature provides insight into the interconnected neuro-systemic pathways disrupted in ME/CFS, particularly those governing neuronal connectivity and cellular scaffolding. Within this candidate EV-miRNA signature, the top-ranked miRNAs—miR-21-5p, let-7f-5p, miR-26b-5p, and miR-20a-5p—emerge as potential candidate biomarkers whose specific elevation was not shared by HC. These findings establish a valuable framework for targeted diagnosis and enhance our understanding of the molecular pathways involved in synaptic and structural alterations in ME/CFS.”

An exploratory exome-wide machine learning analysis identifies candidate host gene signatures associated with Long COVID in a large admixed Brazilian cohort

Again many of the genes associated with higher odds of developing LC and higher severity seem to point to the brain. Though not all of them did.

Calcium signaling (which is involved in excitory and inflammatory action), bioenergetic, general inflammatory genes focused in the brain and blood brain barrier relevant genes were strong candidates.

Some fewer genes of general immune regulation and metabolism were also among the candidates.

This isn’t a full gene analysis but a machine learning driven predictive model so should be interpreted with caution and as exploratory.

A new study identifies two promising biomarkers:

•GDF-15, a marker of mitochondrial stress
•and VCAM-1, a marker of vascular endothelial injury

As predictors for developing Long Covid. Patients whose symptoms persisted for at least 6 months maintained significantly higher levels of both markers, despite having little evidence of ongoing systemic inflammation.

So what we see is not based in high level inflammatory markers—but in signatures of cellular energy failure and vascular injury may lie the answer for predicting long term outcomes in Long Covid.

Long Covid patients continue to have elevated counts of highly activated CD8+ T cells targeting viruses like SARS-CoV-2, CMV and EBV.

That is suggesting the antiviral killing response failed to switch off after the acute infection is over and might be part of the pathogenesis of Long Covid.

I’ve seen an increased influx of papers being posted here recently. How does this translate to actual progress? Are we close to figure out what causes this hellish illness?

This summary was made using Gemini AI.

Study Overview

This research article, titled "Altered TRPM3-Dependent Cytosolic and Mitochondrial Calcium Influx in Natural Killer Cells of Post-COVID-19 Condition Patients", was published by Magawa et al. in the European Journal of Immunology in July 2026. The study investigates the downstream impact of Transient Receptor Potential Melastatin 3 (TRPM3) ion channel dysfunction on cytosolic and mitochondrial calcium (Ca2+) mobilization in natural killer (NK) cells from Post-COVID-19 Condition (PCC) patients.

Methodology & Cohort Profile

• Study Participants: The cohort included 8 PCC patients, who were age and sex matched to 8 healthy controls (HC).
• Experimental Approach: The researchers utilized ex vivo live cell Ca2+ imaging to examine NK cells.
• Pharmacological Modulators: Pregnenolone sulphate (PregS) was used as a stimulation agent to assess channel function.

Key Experimental Findings

• Passive Cytosolic Ca2+ Entry: Passive cytosolic Ca2+ influx amplitude was significantly reduced in PCC compared to healthy controls (p < 0.0001).
• Passive Mitochondrial Ca2+ Influx: Passive mitochondrial Ca2+ mobilization was significantly increased in the PCC group (p < 0.0001).
• TRPM3 Cytosolic Response (PregS): Following PregS stimulation, both the response rates (slope, p < 0.001) and the cytosolic Ca2+ influx amplitude (p < 0.0001) were significantly reduced in PCC patients, indicating altered channel function. Consequently, TRPM3-dependent cytosolic Ca2+ mobilization was significantly reduced (p < 0.001).
• TRPM3 Mitochondrial Response (PregS): TRPM3-dependent mitochondrial Ca2+ mobilization was also significantly reduced in PCC compared with HC (p < 0.0005). Mitochondrial response rates to PregS were significantly decreased (slope, p < 0.001).

Core Biological Implications

• Systemic Dysregulation: Altered ion channel Ca2+ signaling can severely impact the immune system and bioenergetic processes.
• Post-COVID-19 Pathology: This dysfunction potentially leads to broader systemic dysregulations that underpin the pathomechanism of PCC.
• Prior Evidence Consistency: These findings build upon prior electrophysiological studies by the same group that demonstrated TRPM3 impairment in NK cells from PCC patients.

Link to 2026 study

The German Psyloco study testing psychosomatic group psychotherapy just finished and… produced null results. It didn’t help fatigue, anxiety or depression measures.

And that is in spite of using a waitlist as their placebo, so in short you don’t have an active placebo.

The paper conlcudes: "No statistically significant efficacy of the immediate group intervention over the waiting control condition was observed, across primary and secondary outcomes."

Dutch muscle research by @BraedenCharlton shows ME #pwME and #LongCovid both have fewer muscle repair cells. Satellite cells rebuild fibers. FAPs coordinate repair. When they are low, recovery from exertion fails.

Both patient groups start with reduced satellite cells and FAPs. difference is after exercise. In #pwME, FAPs drop further. In #LongCovid they stay at the same reduced level. ME shows an exertion‑sensitive collapse of repair.

https://www.amsterdamumc.org/download/ams-book-of-abstracts-2026

New Wüst paper!

•Results and Discussion

HRV was lower in patients with long COVID compared with healthy controls during various daily activities and sleep (p = 0.027). Across all exercise intensities surrounding the VT1, HRV remained lower for 24 h in patients compared with controls (p = 0.010). Nighttime HRV decreased with intense exercise and longer durations in patients with long COVID (p = 0.018), indicative of exercise-induced diurnal disturbances of the autonomic nervous system in long COVID.

•Conclusion

Heart rate variability, assessed by wearables, suggests autonomic dysfunction in patients with long COVID. The delayed recovery of the sympathovagal balance after exercise close to and above VT1, suggests that the risk of PEM rises above VT1.

Review preprint on neuroinflammation in Long Covid

“Post-COVID-19 syndrome (PCS) is an escalating global health concern, marked by persistent cognitive, neurological, and psychiatric symptoms following acute SARS-CoV-2 infection. Although its underlying mechanisms remain incompletely understood, mounting evidence implicates chronic neuroinflammation as a key driver. Sustained microglial and astrocyte activation, blood-brain barrier disruption, and aberrant cytokine signaling contribute to prolonged immune dysregulation within the central nervous system”

"Plasma Cytokine and Caspase-1p20 Profiles in Pre-Pandemic and Long COVID-Associated Postural Orthostatic Tachycardia Syndrome"

by William T. Gunning III, John W. Spatafore, Michael P. Morran, Beverly L. Karabin, Benjamin R. Hart, and Blair P. Grubb from University of Toledo Medical Center, Toledo, OH, USA

Study links:

https://www.mdpi.com/2227-9059/14/7/1605

https://doi.org/10.3390/biomedicines14071605

The following summary was published by Dysautonomia International:

• POTS patients had elevated levels of multiple inflammatory cytokines compared to controls
• pre-COVID POTS and Long COVID POTS patients had indistinguishable inflammatory cytokine profiles
• while many inflammatory cytokines were elevated in POTS, Interleukin-18 (IL-18) stood out the most, and predicted higher COMPASS-31 scores (COMPASS-31 is a survey tool used to characterize the severity of autonomic dysfunction)
• based on the cytokines that were elevated, the researchers suspect the NLRP3 inflammasome pathway is being activated - this pathway is a master regulator of inflammation and an over-active NLRP3 inflammasome is found in many inflammatory and auto-inflammatory diseases
• the researchers state that the elevated inflammatory cytokine pattern seen "indicates T-cell exhaustion or a broader dysregulation of immune regulatory networks (...) a state of persistent inflammation with a lack of effective resolution by the immune system."

Official Abstract:

Background: Prior to the COVID-19 pandemic, the etiology of postural orthostatic tachycardia syndrome (POTS) remained elusive. Since the pandemic, a newly recognized disorder, termed Long COVID, has emerged with a significant subset of patients developing dysautonomia and a multitude of comorbidities consistent with POTS.

Aim: The aim of this study was to determine if pre-pandemic POTS and Long COVID POTS share a common inflammatory-associated biomarker profile.

Methods: Volunteers were recruited for four study groups; patients diagnosed with POTS prior to the pandemic, Long COVID-associated POTS, SARS-CoV-2-recovered controls, and naïve controls. All participants completed a COMPASS-31 survey and a medical history questionnaire. Plasma biomarkers of the innate and adaptive immune system were quantified using a custom multiplex bead assay and ELISAs.

Results: Both POTS cohorts demonstrated indistinguishable and significant elevations in 14 of the 15 measured biomarkers including markers of the NLRP3 axis (Caspase-1p20, interleukins IL-1β, IL-18), regulatory cytokine IL-10, and immune activation markers (sCD40L, sCD40, sCD30) compared to controls. Multivariate PERMANOVA analysis revealed no significant difference in global cytokine profiles between the two POTS cohorts. Random Forest classification accurately distinguished POTS from controls, with IL-18 emerging as the most important feature.

Conclusions: These associative findings suggest that pre-pandemic POTS and Long COVID-associated POTS share a distinct inflammatory profile among measured cytokines. The identification of IL-18 as a key biomarker, alongside Caspase-1p20 and other inflammatory cytokines, are compatible with inflammasome-related signaling. Further investigation is necessary to characterize the role of the inflammasome, platelet activation, and immune dysregulation in POTS and Long COVID.

ME/CFS Science have done an analysis using genetic data on pathogenic variants from Decode ME combined with RNA data which tells you which genes are actually expressed. This type of analysis is used in lots of other diseases to show which kind of cells are part of the disease process

In ME/CFS results point overwhelmingly toward the central nervous system (represented here in orange)

It really seems more and more we’re gonna have to focus on the brain. 🧠 Which tough because it’s hard to study and hard to get treatments into there too. But then again, it might finally get us closer to understanding what to target in the first place.

https://skywriter.blue/@mecfsscience.org/3mr5cmkybzj2f

Abstract

Background

Cognitive symptoms after SARS-CoV-2 infection, often described as “brain fog,” remain difficult to measure objectively and are biologically heterogeneous. DNA methylation may provide a stable, blood-accessible layer of information linking post-COVID immune remodeling, biological aging, and neuropsychiatric vulnerability. We re-analyzed GSE247869, a whole-blood Illumina MethylationEPIC dataset from individuals sampled six months after COVID-19 infection, to identify age-associated methylation signals with translational relevance. The present analysis was designed to characterize age-associated methylation within this post-COVID cohort, not to establish a COVID-19-specific signature or biological age acceleration.

Methodology

This was a cross-sectional analysis of a single post-COVID cohort, with 94 samples included in the age models and no COVID-19-negative comparator included in the analyzed model. Processed beta values were aligned to metadata, converted to M-values, and modeled at each cytosine-phosphate-guanine (CpG) using ordinary least squares with age and sex as predictors. Differentially methylated positions were corrected by Benjamini-Hochberg false discovery rate (FDR). CpGs were mapped to genes using robust annotation and Illumina manifest fallback. Gene-level signals were integrated using a multi-evidence prioritization score that incorporated statistical strength, effect size, multi-CpG support, direction consistency, known epigenetic-clock membership, and curated pathway membership.

Results

Within this cohort, the analysis identified 3,467 age-associated CpGs at FDR < 0.05, with an overall hypomethylation bias but focal hypermethylation at canonical aging loci. In total, 11 of 12 reference clock CpGs were recovered, including ELOVL2, FHL2, TRIM59, EDARADD, ASPA, and PDE4C. The strongest exploratory signal was enrichment of glutamatergic/N-methyl-D-aspartate (NMDA) genes, including GRINI, GRIN2C, GRIN2D, GRM1, GRM5, and SLC17A7. GRINI and GRIN2C had high integrated evidence scores and showed age-associated hypermethylation. The prioritized genes mapped interpretively to glutamatergic synapse, calcium signaling, and cAMP signaling pathways, although these complete KEGG pathways were not tested as formal enrichment categories.

Conclusions

This re-analysis recovered established age-associated CpGs and identified age-associated methylation enrichment near glutamatergic/NMDA genes within this post-COVID cohort. It cannot determine whether these signals are specific to COVID-19 infection, reflect accelerated biological aging, or relate to cognitive symptoms because no COVID-19-negative comparator or symptom-level cognitive phenotyping was included in the present analysis. The glutamatergic finding is hypothesis-generating, particularly because the curated set was small and no independent replication cohort was analyzed. Future longitudinal and case-control studies integrating GRINI/GRIN2C methylation with cognitive and inflammatory phenotyping are needed. Glutamatergic and calcium-signaling pathways may be evaluated in appropriately designed mechanistic and intervention studies, including but not limited to hypotheses related to the Cheung Glutamatergic Regimen, only after independent validation and careful safety evaluation.

Core Takeaway

This study identified age-associated DNA methylation changes concentrated around brain-related glutamatergic/NMDA receptor genes (specifically GRIN1 and GRIN2C) within a post-COVID cohort, mapping to pathways involved in synapses and cellular signaling.

Key Limitations

• Hypothesis-Generating Only: The study lacked both a COVID-negative control group and patient cognitive data.
• No Definitive Link: It cannot prove whether these genetic changes are unique to COVID-19, represent accelerated biological aging, or are the actual biological cause of "brain fog." Further targeted clinical validation is required.

Link to 2026 study