Evidence map›Paper›PMID 42589652›Full record

Observational studyInternational journal of molecular sciences2026

Haptoglobin Phenotypes Stratify Post-Exertional Cognitive Dysfunction Associated with Altered Cerebral Oxygenation and Metabolic Signatures in Long COVID.

Atefeh Moezzi, Wesam Elremaly, Corinne Leveau, Anita Franco, Oleg Nepotchatykh, Christopher W Armstrong, Alain Moreau

Abstract readObservational Study
In one paragraph

Observational study in International journal of molecular sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Atefeh MoezziDepartment of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada.ORCID 0000-0001-5549-6603
Wesam ElremalyViscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada.ORCID 0000-0002-3577-3551
Corinne LeveauDepartment of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada.
Anita FrancoViscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montreal, QC H3T 1C5, Canada.ORCID 0000-0001-5950-8261
Oleg NepotchatykhPO-Laboratories, Montreal, QC H4T 2A3, Canada.ORCID 0009-0000-5512-6047
Christopher W ArmstrongDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biochemistry Institute, University of Melbourne, Parkville, VIC 3010, Australia.ORCID 0000-0002-5964-5618
Alain MoreauDepartment of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC H3C 3J7, Canada.ORCID 0009-0002-1144-6174

Funding

Montreal TransMedTech InstituteOpen Medicine Foundation CanadaPatient-Led Research Collaborative
6 · The paper itself

Abstract

Long COVID (LC) is a heterogeneous post-infectious syndrome characterized by persistent symptoms, yet the biological basis underlying its interindividual variability remains poorly understood. Given the clinical overlap between LC and myalgic encephalomyelitis (ME), and prior demonstration that haptoglobin (Hp) phenotypes modulate symptom severity in ME, we investigated whether Hp phenotypes similarly stratify post-exertional cognitive dysfunction in LC. In this longitudinal observational study, 44 individuals with LC and 20 short-course COVID controls, who recovered rapidly from SARS-CoV-2 infection without persistent symptoms or sequelae, underwent Hp phenotyping alongside metabolomic and physiological profiling before and after a standardized 90 min passive post-exertional challenge. Hp phenotypes identified clinically distinct LC subgroups. Compared with Hp1-1 individuals, Hp2 allele carriers exhibited greater fatigue, poorer physical function, and more severe post-exertional symptoms. Immediately following the challenge, Hp2-2 participants with LC showed significant cognitive decline, whereas Hp1-1 individuals demonstrated cognitive resilience and more favorable longitudinal cognitive trajectories. This differential susceptibility was accompanied by higher post-exertional cerebral fractional tissue oxygen extraction in the right hemisphere in Hp1-1 individuals and by distinct metabolic signatures, with Hp2 allele carriers exhibiting lower post-exertional plasma concentrations of citric acid, isethionate, and glucosamine. Lower metabolite levels were associated with poorer cognitive performance. These findings support Hp phenotypes as promising candidate biomarkers for biological stratification in Long COVID, pending validation in larger independent cohorts.

Indexed as

BrainCognitive DysfunctionCOVID-19HaptoglobinsOxygenAdultFemaleHumansLongitudinal StudiesMaleMiddle AgedPhenotypePost-Acute COVID-19 SyndromeSARS-CoV-2HaptoglobinsOxygenbiomarkerscerebral oxygenationcognitionhaptoglobin phenotypeslong COVIDmetabolomicspost-COVID-19 conditionpost-exertional malaiseprecision medicine

Identifiers

PMID42589652
PMCPMC13466397

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.