Evidence map›Paper›PMID 40025839›Full record

ArticleJournal of medical virology2025

Genetic Landscape and Mitochondrial Metabolic Dysregulation in Patients Suffering From Severe Long COVID.

Kristoffer Skaalum Hansen, Sofie Eg Jørgensen, Cagla Cömert, Berit Schiøttz-Christensen, Peter Bross, Jane Agergaard, Steffen Leth, Lars Østergaard, Johan Palmfeldt, Rikke Katrine Jentoft Olsen and 1 more

Abstract read
In one paragraph

Article in Journal of medical virology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

11 authors.

Kristoffer Skaalum HansenDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.ORCID 0000-0002-0902-352X
Sofie Eg JørgensenDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Cagla CömertDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Berit Schiøttz-ChristensenDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Peter BrossDepartment of Clinical Medicine, Research Unit for Molecular Medicine, Aarhus University, Aarhus, Denmark.
Jane AgergaardDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Steffen LethDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Lars ØstergaardDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Johan PalmfeldtDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Rikke Katrine Jentoft OlsenDepartment of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Trine H MogensenDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Funding

This study was supported by Aarhus County Research Initiative, Undine, Horizon Europe 2021, and Novo Nordisk Fonden. Novo Nordisk Foundation grants (NNF21OC0066984), (NNF21OC0067157), (NNF20OC0064890 (LØ, THM), Horizon Europe 2021 grant (HORIZON-HLTH-2021-857), (DISEASE-04-07), UNDINE grant 101057100 (THM), Danish Innovation Fund (PASCAL-MID (8056-00010B) (THM)), Danish National Research Foundation (DNRF164 (CiViA)), and Aarhus County Research Initiative (JP, RKJO).
6 · The paper itself

Abstract

Long COVID represents a significant global health challenge with an unclear etiology. Alongside accumulating evidence of mitochondrial dysfunction in patients with acute SARS-CoV-2 infection, a symptomatic overlap exists between long COVID and mitochondrial disorders. However, the genetic underpinnings of mitochondrial dysfunction in long COVID have not been previously explored. We employed whole genome sequencing to analyze 13 patients with severe long COVID to identify genetic defects related to mitochondrial function. We performed extracellular bioenergetics flux analysis on peripheral blood mononuclear cells and proteomics to evaluate cellular bioenergetics and compared the results to those of healthy controls. Our investigation identified 10 variants classified as pathogenic or likely pathogenic and 83 variants of unknown significance affecting a wide range of mitochondria-associated biological functions. Bioenergetics flux analysis in peripheral blood mononuclear cells revealed an altered ATP production rate in four long COVID patients compared to healthy controls. This study presents initial evidence of a potential underlying genetic predisposition to mitochondrial dysfunction in long COVID while demonstrating altered cellular energy capacity in a subset of these patients. These findings open avenues for further research into the role of mitochondrial dysfunction and pathology in patients suffering from long COVID and may pave the way for targeted therapeutic strategies aimed at mitigating mitochondrial dysfunction.

Indexed as

COVID-19MitochondriaMitochondrial DiseasesAdultAgedEnergy MetabolismFemaleGenetic Predisposition to DiseaseHumansLeukocytes, MononuclearMaleMiddle AgedPost-Acute COVID-19 SyndromeSARS-CoV-2Whole Genome SequencingbioenergeticsCOVID‐19inborn error og immunitymitochondriasequelaewhole genome sequencing

Identifiers

PMID40025839
PMCPMC11873671

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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.