Miscellaneous Research Thread

Light-Evoked Neural Activation Patterns in Gulf War Illness: Associations with Symptom Burden
Jonghoon Chang; Alex Hattenhauer; Luisa Saccaro; Shyamal Raolji; David Valdes Arias; Loralei Ann Parchejo; Mireya Hernandez; Brandon Chou; Brinna Desai; Robby Mattes; Elizabeth R Felix; Eric Moulton; Anat Galor
Purpose
Gulf War Illness (GWI) is a chronic, multi-symptom condition affecting veterans of the 1990–1991 Gulf War with reported symptoms spanning across six domains: neurologic/cognitive/mood, fatigue/sleep, pain, gastrointestinal, respiratory, and skin. Prior studies have found light sensitivity in veterans with GWI compared to controls. As the pathophysiology of GWI symptoms and light sensitivity remains unclear, this study investigates symptoms of GWI using the eye as a window to the brain, specifically examining photosensitivity as a potential biomarker of central nervous system dysfunction using light-evoked functional magnetic resonance imaging (fMRI) as a proxy.

Methods
GWI status was determined using the Kansas case definition, in which “Kansas-positive” (Kansas+) is defined as having one or more moderate or severe symptoms in ≥3 domains on the Kansas questionnaire. Of 23 total subjects, 13 participants were classified as Kansas+ and 10 as Kansas-negative (Kansas–). fMRI data from all 23 participants were analyzed, leveraging blood oxygen level-dependent (BOLD)-based responses to infer neural activity. A bright-screen versus black-screen paradigm was used to elicit light-evoked activation. Participants viewed alternating black (~0.5 lux) and white (~65 lux) screens, with sixteen 6-second white-screen periods presented and separated by variable intervals of 51–66 seconds. Group-level fixed-effects analyses were performed in FSL using a generalized linear model. The voxel wise significance threshold was Z > 2.3 (uncorrected for multiple comparisons).

Results
Study participants had a mean age of 60.4 ± 4.8 years, and 78% were male. The Kansas+ group showed greater activation, compared to the Kansas- group, across multiple cortical regions, including the left occipital pole (Zmax = 5.83, p = 0.001). Visual inspection of Kansas+ > Kansas- activation also revealed increased activity in the primary somatosensory cortex BA1 L (Z = 2.75), right insula (Z = 3.00), cingulate gyrus (Z = 3.11), left caudate (Z = 3.05) and left ventrolateral prefrontal cortex (Z = 3.25).

Conclusions
Kansas+ veterans demonstrated greater light-evoked activation in visual cortex and in regions involved in sensory–affective pain processing compared to Kansas– veterans. These exploratory findings suggest that light-evoked fMRI may capture central nervous system alterations relevant to symptom burden in Gulf War Illness.

This abstract was presented at the 2026 ARVO Annual Meeting, held in Denver, CO, May 3-7, 2026.
Web | Investigative Ophthalmology & Visual Science | Abstract
 

The Retina: A Window on Neurodegeneration

New evidence links Chlamydia pneumoniae to retinal inflammation patterns associated with neurodegeneration
theophthalmologist.com theophthalmologist.com

The Retina: A Window on Neurodegeneration​

New evidence links Chlamydia pneumoniae to retinal inflammation patterns associated with neurodegeneration
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A Cedars-Sinai study published in Nature Communications in January 2026 has indicated that chlamydia pneumoniae, the common bacterium which can cause respiratory infections such as bronchitis and pneumonia, could also potentially be used as a retinal biomarker for Alzheimer’s disease and other neurodegenerative diseases.

To learn more, we spoke with authors Maya Koronyo-Hamaoui and Timothy R. Crother about their study findings.
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What would be the single most important takeaway from your study?​

The retina can reflect biologically meaningful Alzheimer’s-related inflammatory pathways, including pathogen-associated innate immune activation, and therefore offers a powerful, accessible window into mechanisms that may contribute to neurodegeneration in a subset of patients.

For ophthalmologists, the key message is that the eye may provide actionable information for cross-disciplinary risk assessment and longitudinal monitoring, once validated and standardized, supporting closer collaboration with neurology in aging care.

Is there anything else you would like to add?​

Two important points. First, our findings do not imply that all Alzheimer’s disease is driven by infection; rather, they support the concept of biological heterogeneity and suggest that infection-triggered inflammasome activation may represent one contributory pathway in a subset of patients. Second, translation should be careful and evidence-based: retinal biomarkers are promising, but specificity, confounders, and clinical utility must be established before routine adoption.

We are enthusiastic about the potential for multi-modal approaches, integrating retinal imaging with systemic biomarkers and clinical phenotyping, to improve early detection, stratification, and eventually precision prevention/intervention strategies.
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Identification of Chlamydia pneumoniae and NLRP3 inflammasome activation in Alzheimer’s disease retina, 2026, Gaire et al.
Gaire, Bhakta Prasad; Koronyo, Yosef; Vit, Jean-Philippe; Hutton, Alexandre; Subedi, Lalita; Fuchs, Dieu-Trang; Swerdlow, Natalie; Rentsendorj, Altan; Shahin, Saba; Martinon, Daisy; Robinson, Edward; Ljubimov, Alexander V.; Schneider, Julie A.; Schneider, Lon S.; Hawes, Debra; Graham, Stuart L.; Gupta, Vivek K.; Mirzaei, Mehdi; Black, Keith L.; Meyer, Jesse G.; Arditi, Moshe; Crother, Timothy R.; Koronyo-Hamaoui, Maya

Abstract​

Chlamydia pneumoniae is an intracellular bacterium implicated in Alzheimer’s disease (AD), but its role in retinal pathology and disease progression is unclear.
Here we identify Chlamydia pneumoniae inclusions in the retina, showing higher burden in AD retina and brain, increasing with APOEε4, disease stage, and cognitive deficit. Retinal and cortical proteomics reveal bacterial-infection and related NLRP3-inflammasome pathways.
Retinal NLRP3 is elevated in mild cognitive impairment and activated in AD dementia, evidenced by increased caspase-1, cleaved interleukin-1β, and cleaved N-terminal gasdermin-D. Chlamydia pneumoniae associates with amyloid-β42, inflammation, apoptosis, pyroptosis, and AD status.
In neuronal cultures and APPSWE/PS1ΔE9 model mice, infection induces amyloid-β, inflammasome activation, neuroinflammation, and neurotoxicity, and chronic infection worsens cognition.
Fewer pathogen-colocalized microglia are found in AD retinas, implying impaired clearance. Machine learning detects retinal Chlamydia pneumoniae or NLRP3, combined with amyloid-β42, as predictors of AD diagnosis and stage.
These findings support a disease-amplifying role for Chlamydia pneumoniaeand propose NLRP3-attenuation or antibiotic-based early interventions.



Web | DOI | PMC | PDF | Nature Communications
 
Not specifically about ME/CFS, although may have implications for a small subset of severe pwME who are considered to have a "disorder of gut-brain interaction" -

Biopsychosocial Considerations to Avoid and Wean Parenteral Nutrition in patients without intestinal failure: An expert practice and position paper from the European Society of Clinical Nutrition and Metabolism and the Rome Foundation

The European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro-gastroenterology and Motility and the Rome Foundation for Disorders of Gut-Brain Interaction consensus is that parenteral nutrition (PN) should not be prescribed for patients without intestinal failure (IF), where the oral and/or enteral route can be used. In this further expert practice and position paper from ESPEN, biopsychosocial considerations to avoid and wean PN in such patients without IF are described. These include specifically distinguishing between conditions such as chronic intestinal pseudo-obstruction, enteric dysmotility, opioid bowel dysfunction, narcotic bowel syndrome, disorders of gut-brain interaction and eating disorders/disordered eating to positively identify those with evidence of intrinsic small bowel dysmotility that can lead to intestinal failure. A holistic biopsychosocial framing of these conditions with attention to, and management of, pain and sensory, psychiatric, psychological, behavioural and social components beyond a reductionist motility focus, aims to mitigate iatrogenic harm and support more sustainable recovery. The role of limited investigations, their pitfalls and the importance of contextualising medical and psychiatric comorbidities are reviewed. Psychiatric approaches to eating disorders/disordered eating, the use of gut-brain neuromodulators, behavioural therapies and psychosocial strategies to avoid and/or wean PN are detailed. Specific practical approaches to optimising nutritional care are described, including graded food re-exposure. Regular multidisciplinary team reviews ensure clear, consistent messaging, while a cohesive approach across all disciplines reduces burnout and, helps patients feel supported, improving adherence, symptom outcomes and overall healthcare utilisation. Safe and effective weaning from parenteral nutrition requires a structured, compassionate and psychologically informed approach.
 
Nightsong said:
Not specifically about ME/CFS, although may have implications for a small subset of severe pwME who are considered to have a "disorder of gut-brain interaction" -
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I think this is pretty specifically about ME/CFS and I am not at all surprised to see Peter Payne as first author. This is the policy that led to Maeve's death, now agreed Europe wide by a group of faith healers.

Apparently they now have gut/brain neuromodulators too.
 
Nordic track: NIH dysfunction and my Helsinki recruitment, 2026, Brenner et al.

Brenner, Charles

Abstract​

National Institutes of Health aims to prioritize groundbreaking work that challenges existing views with rigor and reproducibility, and shows potential for translation.
Increasingly, however, reviewers penalize applicants for novelty, critique of dogma, and for having work translated, while program officers are now guided to refuse review of proposals on forbidden topics.
These practices have the potential to substantively degrade U.S. biomedical progress and played a role in my laboratory’s move to Europe.

Web | DOI | Trends in Endocrinology & Metabolism
 
Nightsong said:
Not specifically about ME/CFS, although may have implications for a small subset of severe pwME who are considered to have a "disorder of gut-brain interaction" -

Biopsychosocial Considerations to Avoid and Wean Parenteral Nutrition in patients without intestinal failure: An expert practice and position paper from the European Society of Clinical Nutrition and Metabolism and the Rome Foundation

The European Society of Clinical Nutrition and Metabolism (ESPEN), the European Society of Neuro-gastroenterology and Motility and the Rome Foundation for Disorders of Gut-Brain Interaction consensus is that parenteral nutrition (PN) should not be prescribed for patients without intestinal failure (IF), where the oral and/or enteral route can be used. In this further expert practice and position paper from ESPEN, biopsychosocial considerations to avoid and wean PN in such patients without IF are described. These include specifically distinguishing between conditions such as chronic intestinal pseudo-obstruction, enteric dysmotility, opioid bowel dysfunction, narcotic bowel syndrome, disorders of gut-brain interaction and eating disorders/disordered eating to positively identify those with evidence of intrinsic small bowel dysmotility that can lead to intestinal failure. A holistic biopsychosocial framing of these conditions with attention to, and management of, pain and sensory, psychiatric, psychological, behavioural and social components beyond a reductionist motility focus, aims to mitigate iatrogenic harm and support more sustainable recovery. The role of limited investigations, their pitfalls and the importance of contextualising medical and psychiatric comorbidities are reviewed. Psychiatric approaches to eating disorders/disordered eating, the use of gut-brain neuromodulators, behavioural therapies and psychosocial strategies to avoid and/or wean PN are detailed. Specific practical approaches to optimising nutritional care are described, including graded food re-exposure. Regular multidisciplinary team reviews ensure clear, consistent messaging, while a cohesive approach across all disciplines reduces burnout and, helps patients feel supported, improving adherence, symptom outcomes and overall healthcare utilisation. Safe and effective weaning from parenteral nutrition requires a structured, compassionate and psychologically informed approach.
Click to expand...
Thread made for this paper: Biopsychosocial Considerations to Avoid and Wean Parenteral Nutrition in patients without intestinal failure..., 2026, Paine et al
 
Acceptance and Demand for Teledentistry and the Role of Dental Hygienists, 2026, Son et al.

Son, Seo‐yoon; Kwon, Min‐ji; Park, Ga‐young; Oh, Yun‐seo; Woo, Jin‐sol; Cheon, Yoon‐jeong; Choi, Jin‐sun

ABSTRACT​

Introduction​

In 2020, telemedicine between doctors and patients was temporarily permitted without restrictions as a response to COVID-19.
However, dental telemedicine adoption was significantly lower than in other medical fields, highlighting the need to investigate factors affecting its acceptance.
This study aimed to evaluate the acceptance and demand for dental telemedicine among dental professionals and the general public and examine the roles of dental hygienists in this context.

Methods​

A cross-sectional survey was conducted with 253 participants, including dental hygienists and dentists (with ≥ 1 year of clinical experience), and adults (≥ 19 years old) with prior dental care experience. Data were analysed using IBM SPSS Statistics, version 25.0.

Results​

Significant differences in acceptance were observed among groups (p < 0.001), with higher acceptance in the general public (50.3%) than in dental hygienists (27.1%) and dentists (20.0%).
Over 70% of respondents across all groups recognised the importance of dental hygienists in teledentistry.

Conclusion​

Dental professionals were more concerned about the limitations of dental telemedicine than its benefits.
To facilitate the successful implementation of telemedicine systems in dentistry, establishing clear guidelines and legal frameworks for dental telemedicine is essential.
Additionally, defining the roles and responsibilities of dental professionals, particularly dental hygienists, is crucial to ensuring the effective operation of these systems.

Web | DOI | PDF | International Journal of Dental Hygiene | Paywall
 

Clinical Failure Rates Over the Decades: Yikes​

24 JUL 2026 BY DEREK LOWE
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Here we go: in the 1960s, the clinical failure rate was 90%.
In the 1970s, 81%.
In the 1980s, it was 80%, and in the 1990s it was 88%.
In the 2000s, 91% of all clinical candidates failed, and in the 2010s, it was 91% as well.
I have rounded the decimal points here, because there are of course error bars on these numbers (and those spreads are naturally higher on the older numbers).
But the numbers for the last three decades all lie within the same bounds, so if you quote a failure rate of 91% you cannot be far wrong.
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Need for NAMs: A systematic evidence synthesis revealing over half a century of drug development failure, 2026, Filipova et al.

Filipova, Dilyana; Boomgaarden, Wolfgang; Fox, Leyla; Knight, Andrew; Lickiss, Bettina; Maass, Christian; Neumann, Gaby; Watkins, Justine; Herrmann, Kathrin; Ewart, Lorna; Gossmann, Matthias; Ritskes-Hoitinga, Merel; Zietek, Tamara

Highlights​

  • First synthesis of six decades of clinical drug attrition and reasons for failure.
  • Clinical attrition at ∼80–91% since the 1960s, peaking at ∼91% in the 2000s–2010s.
  • 77% of failures due to biological factors, highlighting limits of animal testing.
  • Findings support the need for human-relevant NAMs in preclinical drug assessment.

Abstract​

Background​

Preclinical assessment of drug safety, efficacy and pharmacokinetics still relies largely on animal‑derived data, despite their limited ability to predict human outcomes.
New Approach Methodologies (NAMs) are emerging as more human‑relevant preclinical tools.
This systematic evidence synthesis examines
(1) current levels and temporal trends in clinical drug attrition and
(2) the proportion of failures attributed to biological factors such as safety, efficacy and pharmacokinetics that are routinely evaluated during preclinical testing, to identify priority areas for NAM implementation.

Methods and Findings​

We systematically searched PubMed on March 5, 2024, for peer-reviewed, English-language studies since 1963 reporting numerical primary data on clinical drug attrition rates and/or reasons for failure.
The protocol was prospectively registered (osf.io/46mw5).
We excluded non-original research and studies on specific cases, diseases, or single drug classes.
Thirty-two publications met the criteria, yielding 60 attrition and 36 failure-reason datasets (1963–2017).
Across six decades, mean clinical attrition ranged from ∼80 to ∼91 % with the highest rates within the past two decades.
Overall, biological factors (safety, efficacy, pharmacokinetics) accounted for ∼77% of reported causes.
Limitations include heterogeneous reporting, restriction to English, and exclusion of grey literature.

Conclusions​

Clinical drug attrition has not improved in the last six decades, peaking at ∼91% in the 2000s–2010s, with most failures linked to biological factors.
These findings suggest that prevailing preclinical approaches – many of which heavily rely on animal models – often have limited ability to predict clinical outcomes and highlight the urgent need for more predictive, human-relevant NAMs.

Keywords​

drug attrition
success rate
likelihood of approval
drug development
reasons for drug failure

Web | DOI | NAM Journal | Open Access

Discussed on Hacker News.
 
Jonathan Edwards said:
Isn't this simply a reflection of investment chance-of-profit statistics. The industry will always try only slightly fewer drugs than causes it to actually make a loss.
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Yes, if it’s about new drugs I would be very surprised if it isn’t primarily due to pharma companies being willing to bet on long shots because the upside is to large.

The same would probably be true to trying to repurpose drugs as well.

One could ask what it says about the 10 % successful ones, because you’d expect 5 % of ineffective drugs to have successful trials just by chance..
 
Beyond Anxiety: School Refusal as a Disrupted Individuation Process in Post-COVID Adolescents, 2026, Brandibas

Brandibas, Gilles

Abstract​

Background​

The post-COVID surge in school refusal has prompted a clinical response overwhelmingly focused on anxiety and its treatments.
While this orientation is scientifically grounded, it remains partial: it fails to account for a dimension that successive lockdowns massively disrupted without the recent literature fully integrating it, namely the separation-individuation process (SIP) specific to adolescence.

Aims​

This article proposes a complementary and integrative reading of post-COVID school refusal, organized around three axes.

Approach​

First, lockdowns interrupted the environmental conditions necessary for the SIP to unfold, producing a developmental regression whose extent was revealed upon the return to school.
Second, the hyperdigitalization that followed the lockdowns offered adolescents a substitution space enabling pseudo-separation without genuine individuation, durably impeding the process.
Third, internal working models of attachment constitute the vulnerability substrate within which these impediments take hold.

Findings​

A clinical vignette illustrates these articulations through a composite case of an adolescent whose partial school refusal is reread as an attempt to regulate a disrupted SIP rather than as an anxiety symptom to be reduced.

Conclusions​

The article argues for a non-pathologizing reading of school refusal and opens research perspectives on the relationship between autonomy, attachment, and digital practices in adolescence.

Plain Language Summary​

Since the COVID-19 pandemic, many more young people are refusing to attend school.
Most explanations focus on anxiety (and anxiety-based treatments such as cognitive-behavioral therapy are indeed helpful for many).
But they do not explain everything, and a significant proportion of young people do not respond to these approaches.
This article proposes a complementary explanation: for many adolescents, school refusal after COVID-19 is not primarily an anxiety problem (it is a disrupted growing-up process).
Adolescence is a time when young people need to gradually separate from their family environment and build their own identity.
This process requires access to spaces outside the family (school, peer groups, social activities).
Successive lockdowns brutally removed these spaces, forcing adolescents back into the family home at precisely the moment when they needed to move away from it.
At the same time, the massive increase in screen use during lockdowns offered adolescents a substitute world (social networks, online gaming, short videos) where they could feel socially present without actually leaving home.
This digital withdrawal felt like independence, but it was not: it deferred the real work of growing up without replacing it.
When schools reopened, many adolescents found themselves having to resume this growing-up process from an earlier stage, without the inner resources to do so.
School refusal, in this reading, is less a symptom to eliminate than a signal that something important is being negotiated (and that this negotiation needs support, not just symptom reduction).
The article illustrates this through the case of a 15-year-old boy, and concludes with practical suggestions for school psychologists and clinicians working with adolescents who refuse school.


Web | DOI | PDF | Clinical Child Psychology and Psychiatry | Paywall
 
Representations of the intrinsic value of information in mouse orbitofrontal cortex (2026)

Animals are motivated to seek information that does not influence reward outcomes, suggesting that information has intrinsic value. Here we have developed an odor-based information seeking task that reveals that mice choose to receive information even though it does not alter the reward outcome. Moreover, mice are willing to pay for information by sacrificing water reward, suggesting that information is of intrinsic value to a mouse.

We used a microendoscope to reveal neural activity in the orbitofrontal cortex (OFC) while mice learned the information seeking task. We observed the emergence of distinct representations of odors predictive of information and odors predictive of water reward. A latent variable model recapitulated these different representations in the low-dimensional dynamics of OFC neuronal population activity.

These data suggest that mice have evolved separate pathways to represent the intrinsic value of information and the extrinsic value of water reward. Thus, the desire to acquire knowledge is observed in mice and the value of this information is represented in the OFC. The mouse now provides a facile experimental system to study the representation of the value of information, a higher cognitive variable.

Web | PDF | Nature Neuroscience | Open Access

Perhaps the simplest explanation argues that information led, at some time during the evolution of a species, to extrinsic value. Indeed, in natural environments, knowledge improves an organism’s model of the world, and its acquisition improves decision making and augments survival. This quest for information may therefore have been fixed by selection and now generalizes to circumstances in which the acquisition of knowledge may be of no extrinsic value. This model suggests that the desire for knowledge evolved by assigning innate pleasure to the acquisition of information. Thus, the value of information may ultimately reflect the pleasure it provides.
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Abstract:

Chronic fatigue among healthcare staff at Farhat University Hospital Hached, Sousse, Tunisia
Ghammam, R.; Kalboussi, H.; Ben Fredj, S.; Ben Saad, O. K.; Zammit, N.; Skhiri, A.; Chouikha, F.; Erguez, A.; Akrimi, R.; Belguith, W.; Chouchene, A.; Jihene, M.; Harrabi, I.
Introduction
Chronic fatigue is common symptom that may affect individuals’ life. This condition is particularly concerning among health care workers and may affect their mental health and well-being.

Objectives
Our study aimed to measure the proportion of fatigue chronic syndrom among health workers and its associated factors.

Methods
A cross-sectional was performed among a random sample of healthcare workers at univesity Hospital Farhat Hached Sousse Tunisia. We excluded all professionals presetting severe chronic conditions. Fatigue chronic syndrome was accessed using chronic fatigue syndrome scale (FCS). Life quality was measured using SF12 questionnaire and depression using PHQ9 form.

Results
Our population consisted of 205 participants, including 89.3% men. The sex ratio M/W was 0.12. Participants were 18% medical doctors, 1.5% nursing assistants, 42.4% nurses and 38% health technicians.

Chronic fatigue syndrome (CFS) affected 11.2% of participants. Among health workers, 4.4% presented CSF like with insufficient fatigue and 22% chronic idiopathic syndrome. Among women 12,6% presented a CFS compared to one men (4.5%) (p=0,078). No significant association was found between CFS and night work (P=0,491).

From nurses and health technicians, 12.5% presented a chronic fatigue syndrome compared to 5.4% of doctors without a significant difference (p=0.216). Physical quality of life score was significantly higher among participants with CFS (35.15±6 vs 44.56±8.75, p<0.001). The same result was found for mental quality of life.

CFS group presented Higher score of depression (12.17±5.6) compared to the group with no CFS (5.43±3.92) (p<0.006). No association was observed with vitamin D level.

Conclusions
Chronic fatigue syndrome is prevalent among healthcare workers, with a significant impact on both physical and mental quality of life. Its association with depression underscores the need for proactive support and screening.

Although a non-significant association was observed between vitamin D levels and fatigue, further research with a larger sample size is warranted to clarify this potential link and inform targeted interventions.
Web | DOI | PDF | European Psychiatry | Conference Abstract
 
Abstract:

Antibody Signatures of Illness Trajectories: Comparative FLow-based Immune Profiling (FLIP) in Long COVID 2260564
Kremer, Vanessa; Hansen, Paige; Loeser, Grace; Michaels, Katarzyna; Joughin, Brian; Bradshaw, Christine; Nikolich, Janko; Hornig, Mady; Tal, Michal
Introduction
Infection-associated chronic illnesses (IACIs) such as Long COVID (LC) and Post-Treatment Lyme Disease Syndrome (PTLDS) reveal a gap in our understanding of immune resolution after infection. Some patients experience persistent fatigue, cognitive dysfunction, post-exertional malaise, dysautonomia, musculoskeletal pain, and allergy-like symptomes. Although triggered by distinct pathogens (SARS-CoV-2 for L; B. burgdorferi for PTLD), these conditions share overlapping clinical and immunological features, suggesting convergent pathways of post-infectious immune dysregulation. Current serological assays quantify bulk antibody titers but fail to resolve the functional antibody diversity that may determine recovery versus chronicity–highlighting the need for mechanistic biomarkers of disease trajectory.

Methods
To address this, the Tal Lab developed FLow-based Immune Profiling (FLIP), a high-dimensional serological assay quantifying pathogen-bound antibodies across IgD, IgM, IgA, IgE, and IgG1—4 subclasses using live pathogens or antigen-coated beads as bait. FLIP captures effector-function—relevant antibody heterogeneity, revealing ratiometric patterns that encode immune trajectory. We established FLIP for LC, analyzing plasma from the RECOVER cohort to characterize SARS-CoV-2—specific and total antibody distributions, and compared these with the MAESTRO PTLDS cohort, where FLIP had identified antibody ratios predictive of symptom persistence.

Results
Our results show that (i) FLIP can be adapted to small-particle pathogens (viruses), enabling high-resolution mapping of SARS-CoV-2—specific repertoires, and (ii) distinct ratiometric antibody architectures differentiate recovery from persistence across both patient cohorts, supporting their potential use as predictive biomarkers of post-infectious outcomes.

Conclusion
Our findings establish FLIP as a versatile platform for dissecting humoral immune responses and provide a foundation for predictive diagnostics and immune-targeted interventions in IACIs.
Web | DOI | PDF | The Journal of Immunology | 2026 | Conference Abstract
 
Abstract:

Paediatric long COVID MDT clinic improves school attendance and parent-reported paediatric quality of life, 2026, O’connor et al

O’connor, Mary; Okechukwu, Hannah; Bell, Clare; Lambert, Paula; James, Nicola; Watts, Shelagh
Why did you do this work?
In 2023, a novel multidisciplinary paediatric Long Covid Clinic was established comprising Consultant Paediatrician, Clinical Psychologist, Occupational Therapist, Physiotherapist and Assistant Psychologist, according to NHSE guidelines (NHS England, 2022). This clinic provided holistic assessment, interventions using goal setting and pacing strategies, psychological therapy, and liaison with schools.

Children and young people (CYP) with long covid experience significant functional impairment with resulting impact on school attendance and wellness (Johnston et al., 2023). However, there is still little quantitative research on the benefits and challenges of this type of paediatric service.

What did you do?
CYP with symptoms persisting for more than 12 weeks post-COVID-19 infection were referred from secondary care. Twenty CYPs attended between January 2023 and April 2025. Mean age at first appointment was 13.74 (SD = 2.70). 65% of the CYP were female. Parent reported school attendance percentages were collected at baseline and follow-up. The Paediatric Quality of Life Inventory was used to measure quality of life at baseline and follow-up (Varni et. al, 1999). Depending on patient complexity, the follow-up period ranged between 6 months and 18 months. Data were analysed in SPSS v.17.

What did you find?
School attendance significantly increased from 48.37% (SD 25.44) at baseline to 78.21% (SD 24.58) at follow-up (t(18) = -6.34, p < 0.0001). Parent reported paediatric QoL scores also improved between baseline (M = 42.80, SD = 16.87) and follow-up (M = 57.79, SD = 21.73), (t(12) = -2.31, p < 0.05).

There were no significant differences found between teen reported paediatric QoL scores over time. There were significantly strong correlations between parent and teen QoL scores at both baseline (R = .85, p < .0001) and follow-up (R = .93, p < .0001).

What does it mean?
Our findings suggests that an MDT service model is beneficial for this complex patient group. In their qualitative analysis, Taylor and colleagues found that more than half of CYPs seen in specialist long covid clinics showed functional improvement and increased school attendance over 6 months, while a subgroup had persistent symptoms (2025). School attendance has also been found to increase in CYP attending a similar clinic (Goddings et. al, 2025).

A significant strength of the current study includes the relevant choice of simple outcomes which are meaningful for CYP, and easily replicable for future studies. A high retention rate for follow up school attendance data was notable. The small sample size affects study power, therefore, caution should be exercised when interpreting results. However, an insight into the benefits of an MDT model for Long Covid contributes to an underrepresented area of paediatric research.

Web | DOI | PDF | British Association of General Paediatrics (BAGP) | Conference Abstract
 
Abstract:

Building supportive care post-covid: child and parent perspectives from a new long-COVID clinic, 2026, Okechukwu et al

Okechukwu, Hannah; O’Connor, Mary; Bell, Clare; Watts, Shelagh
Why did you do this work?
The long-term impact of COVID-19 on children and young people (CYP) remains a significant concern in paediatrics. Amongst CYP, Long-COVID contribute to absenteeism, stunted academic progress, isolation, and reduced emotional wellbeing and self-esteem.1 With childhood and adolescence being critical periods for cognitive, social and emotional development, effective support strategies are urgently needed.2

Unfortunately, support is becoming scarce. As of 2025, 62% of 120 UK Long-COVID services face closure or uncertain futures, and only 8 of 13 specialist CYP hubs are set to continue, threatening to exacerbate inequities in care accessibility.3

What did you do?
Recent research has emphasised the importance of sustainable, validating support in the form of school-based adjustments and helping CYP to develop the skills for long-term condition management.4

In September 2021, the paediatrics team at Buckinghamshire Healthcare Trust(BHT) launched a monthly Long-COVID clinic to support local CYP. The multidisciplinary service involves a consultant paediatrician with special interest, physiotherapist (PT), occupational therapist (OT), psychologist, and psychologist assistant, providing holistic care. New patients are assessed in clinic with six-monthly follow-ups, whilst PT, OT, and psychology provide weekly input as needed and liaise with schools to facilitate pacing.

To evaluate service quality, CYP and caregivers were invited to complete satisfaction surveys. This included 4-point Likert scales covering multiple domains of care alongside free-text responses covering best aspects, recommendations, and further comments. Responses were analysed descriptively to identify strengths and areas for improvement.

What did you find?
32 surveys were returned (CYP= 16, Caregivers=16), with 12 of these being paired. Overall satisfaction was high:

94% of CYP and 100% of caregivers rated the clinic ‘very helpful’

94% of both groups felt ‘absolutely listened to’, though fewer CYP(69%) than caregivers(88%) felt fully able to communicate their needs

63% of CYP and 81% of caregivers ‘absolutely agreed’ with ongoing care plans

69% of both groups were ‘very satisfied’ with appointment access and organisation

Qualitative feedback highlighted feeling listened to, encouragement, practical strategies, and timetable adjustments to manage fatigue and support school attendance as key benefits. Normalisation of symptoms and recognition of positive progress also encouraged engagement. Suggested improvements included earlier or more frequent reviews, opportunities for CYP to speak with the team independently, and improved logistics surrounding appointments, such as communication about appointment times and attending professionals.

What does it mean?
The BHT Long-COVID clinic was highly valued by CYP and caregivers, contrasting national data highlighting poor satisfaction and unmet needs for coordinated Long-COVID support.5 The findings underscore the importance of communication, emotional support, practical strategies and school-focused adjustments.

Lower CYP ratings for communicating needs and agreeing with care plans indicate opportunities to strengthen shared decision-making. Despite limitations of small sample size and incomplete pairings, these findings offer valuable patient insights to inform service development and advocate for sustained investment.

Web | DOI | PDF | British Association of General Paediatrics (BAGP) | Abstract
 
Abstract:

Clinician perspectives on the similarities and differences between ME/CFS and long COVID in children and young people, 2026, Bond-Kendall et al

Bond-Kendall, Joanne; Davison-Jenkins, Abi; Campbell, Harriet; Segal, Terry; Luckraz, Kritikat; Siddiqui, Alina; Chikhliwala, Priya; Soroye, Esther; Lee, Joshua
Why did you do this work?
The long-term effects of COVID-19 are still being studied, but clinicians working with Children and Young People (CYP) with Long Covid find that symptoms overlap with those seen in ME/CFS (Chronic Fatigue Syndrome) and tend to see positive outcomes when following similar interventions.1–4 The aim of our surveillance project is to reach a consensus on similarities and differences between the two conditions, from clinicians working with these CYP. We hope that the results of this project will inform diagnosis and management of these conditions, and support decisions about how to provide continued care.

What did you do?
We are using a Delphi methodology to find a consensus between clinicians working with CYP with Long COVID and ME/CFS. Phase 1 of data collection involved structured interviews of 14 multi-disciplinary teams (MDTs) across the UK. The MDTs included paediatricians, physiotherapists, occupational therapists, nurse consultants and psychologists. Overall, 48 clinicians were interviewed (M= 3, F= 45).

We conducted a Thematic Analysis 5 of the interview transcripts, using the themes identified to create a questionnaire of collated statements. In Phase 2, The MDTs will be asked to rate their level of agreement with each statement. Phase 2 is just beginning, and the results will be available at the conference. Agreement among Phase 2 participants will be assessed, and if consensus on the questionnaire is lower than 65%, there will be a third round of data collection. The statements will be sent around again with information on the majority responses. Participants will be given an opportunity to change their answer based on this information.

What did you find?
Phase 1 identified themes within the areas of diagnosis, terminology, trajectories, symptomology, psychosocial influences and effects and management. The responses suggested significant overlap between the two diagnoses in all of these areas, and that the core interventions for managing both conditions are the same. However, clinicians identified some symptoms unique to Long COVID, and some as more severe in Long COVID. The data suggested difficulty distinguishing clinically between Long COVID and ME/CFS, and hence a preference for formulation-based understanding and management. Phase two will enable us to confirm the consensus among these themes.

What does it mean?
A consensus from clinicians clarifying the similarities and differences between Long COVID and ME/CFS will allow for more consistency in diagnosis and management across professionals. These findings are critical in the current context of Long COVID services closing across the UK, supporting the need for CYP with either condition to have access to specialist fatigue services.

Web | DOI | PDF | Young People’s Health Special Interest Group | Abstract
 
Association of omega-3 fatty acids (EPA, DHA, DPA) and vitamin D with mortality and morbidity outcomes in COVID-19 patients: the COMED study, 2026, Bischofová et al.

Bischofová, Svatava; Měřínská, Zuzana; Beňovská, Miroslava; Husa, Petr; Řehůřková, Irena; Klinerová, Jana; Bourková, Ludmila; Horáková, Klára; Dvořáková, Štěpánka; Hoffmannová, Alice; Podborská, Martina; Ruprich, Jiří
Abstract
Background and aims Long-chain omega-3 fatty acids (FAs) and vitamin D (VitD) are implicated in the modulation of immune responses and inflammatory processes within the body. The COMED study evaluated levels of DHA, EPA and DPA (expressed as a modified omega-3 index, mO3I, defined as the percentage of these FAs relative to total FAs in whole blood) and VitD in patients with COVID-19 in relation to mortality and severe disease, as well as additional morbidity-related outcomes, including probability of hospitalisation and length of hospital stay (LOS). Methods A total of 160 patients were enrolled, of whom 28 died during follow-up. Associations between mO3I and VitD levels and clinical outcomes were analysed using logistic and linear regression models adjusted for age, sex, BMI, smoking, diabetes mellitus, and hypertension. Results Higher mO3I levels (Q4 ≥ 6.39%) were associated with lower odds of death (OR = 0.24, 95% CI: 0.05–0.87) and lower probability of hospitalisation (OR = 0.28, 95% CI: 0.09–0.91) compared with lower mO3I levels (Q1–Q3). Higher VitD levels (Q4 ≥ 71.9 nmol/L) were associated with a shorter LOS by 2.19 days compared with Q1–Q3, while higher levels (Q2–Q4 > 36.7 nmol/L) shortened LOS by 2.96 days compared with Q1. Age was the strongest predictor of mortality, severe disease, and LOS; BMI increased the probability of severe disease; smoking prolonged LOS. Conclusion Higher mO3I levels were associated with lower odds of death, with similar trends observed for hospitalisation, whereas higher VitD levels were associated with a shorter LOS. Nutritional biomarkers and modifiable lifestyle factors, such as body weight and smoking, were associated with differences in clinical outcomes in COVID-19. However, the observational design of the study precludes causal interpretations.

Web | DOI | PMC | PDF | Frontiers in Nutrition | Open Access
 
Expanding the human proteome with microproteins and peptideins, 2026, Deutsch et al

Abstract

"A major scientific drive is to characterize the protein-coding genome, which is a primary basis for studying human health. But the fundamental question remains of what has been missed in previous analyses. Over the past decade, the translation of non-canonical open reading frames (ncORFs) has been observed across human cell types and disease states1,2,3, with major implications for biomedical science. However, a key gap in knowledge has been which ncORFs produce small microproteins or alternative protein molecules that contribute to the human proteome.

Here we report the collaborative efforts of the TransCODE Consortium4 to produce a consensus landscape of protein-level evidence for ncORFs. We show that about 25% of a set of 7,264 ncORFs gives rise to detectable peptides in a large-scale analysis of 95,520 proteomics experiments. We develop an annotation framework for ncORF-encoded microproteins as human proteins and codify the new conceptual model of ‘peptideins’ as microproteins that have indeterminate potential as functional proteins.

To probe the biological implications of peptideins, we create an evolutionary analysis approach, termed ORF relative branch length (ORBL), and determine that evolutionary constraint is common and associates with observation of ncORF-derived peptides. We then characterize a pan-essential cellular phenotype for one peptidein from the OLMALINC long non-coding RNA.

Overall, we generate public research tools supported by GENCODE and PeptideAtlas and advance biomedical discovery for understudied components of the human proteome."

Article about the paper:
Revealed: the mysterious ‘dark’ proteins that might play a big role in biology (archive)
 
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