Genetic Landscape and Mitochondrial Metabolic Dysregulation in Patients Suffering From Severe Long COVID, 2025, Hansen et al

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.

Link | PDF (J. Med. Virol., March 2025, open access)

 

The patient cohort consisted of 13 participants included at the long COVID Clinic at Aarhus University Hospital, Denmark. All participants had prior polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection and were diagnosed with long COVID by infectious disease specialists. The participants were selected from a previous clinical trial cohort at our study site [17].

17 is this:
https://www.s4me.info/threads/high-...se-2-crossover-trial-2022-hansen-et-al.30299/

It was a well-run trial of Q10 with negative and accurately reported results.

 

Doesn't look like too much to me?

They checked 94 million genetic variants in patients, found 398 differnt mitochondrial ones in patients, there was one pathway that had variants in five/13 patients, being the Mucin von willebrand pathway.