Multi-omics analysis of long COVID reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune..., 2026, Tasoula

[Dolphin]

Frontiers | Multi-omics analysis of long COVID (post-COVID-19 condition) reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune dysregulation

IntroductionPost-COVID Syndrome (PCS), or long-COVID, is a major public health burden, but its underlying mechanisms remain poorly understood. Because acute ...

www.frontiersin.org

ORIGINAL RESEARCH article​

Front. Immunol., 21 May 2026

Sec. Viral Immunology

Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1776555

Multi-omics analysis of long COVID (post-COVID-19 condition) reveals persistent mitochondrial dysfunction, suppressed oxidative phosphorylation, and immune dysregulation​

• E
  Ethan Waisberg 4

• 1. Guarnieri Research Group LLC, Philadelphia, PA, United States
• 2. Ohio University, Heritage College of Osteopathic Medicine, Athens, OH, United States

Abstract​

Introduction:

Post-COVID Syndrome (PCS), or long-COVID, is a major public health burden, but its underlying mechanisms remain poorly understood. Because acute SARS-CoV-2 infection induces marked suppression of mitochondrial oxidative phosphorylation (OXPHOS), we investigated whether persistent immunometabolic remodeling is a recurring transcriptional, metabolic, and proteomic feature of PCS.

Methods:

We performed an integrated multi-omics analysis of transcriptomic, proteomic, and metabolomic datasets across multiple tissues from Syrian hamster models and human cohorts spanning acute infection through post-acute and PCS stages extending up to 12 months post-infection.

Results:

Across species and tissues, we observed overlapping signatures of mitochondrial dysfunction, including sustained suppression of OXPHOS, activation of mitochondrial stress responses, and enrichment of inflammatory pathways. Skeletal muscle exhibited the most pronounced and persistent mitochondrial repression in both hamsters and PCS patient biopsies, consistent with fatigue-associated phenotypes. Hamster heart and kidney tissues also showed persistent OXPHOS suppression, while lung tissue demonstrated prolonged inflammatory signaling despite partial metabolic recovery. In the nervous system, transcriptional profiles revealed region-specific patterns, including persistent cortical mitochondrial repression and partial recovery in sensory-associated regions. Peripheral blood mononuclear cells (PBMCs) transcriptomics and serum metabolic datasets suggested prolonged downregulation of OXPHOS-associated programs up to 12 months post-infection, potentially contributing to persistent immune dysregulation in susceptible individuals with underlying conditions. Longitudinal serum proteomics in PCS patients revealed sustained mitochondrial stress responses, increased oxidative stress signatures, and persistent immune activation at 1 and 6 months post-infection compared to recovered controls.

Discussion:

Together, these multi-omics results identify persistent mitochondrial repression and immune dysregulation as recurring features across PCS-associated datasets, providing a framework linking bioenergetic dysfunction with chronic immune activation and supporting future mechanistic and therapeutic investigation.

Highlights​

• Persistent mitochondrial and immune alterations are observed across multiple tissues in PCS-associated datasets.
• Serum proteomic profiles suggest ongoing mitochondrial stress and immune activation in PCS.
• PCS skeletal muscle shows sustained OXPHOS suppression, consistent with fatigue-associated phenotypes.
• Brain regions exhibit heterogeneous metabolic recovery, with persistent cortical mitochondrial repression observed in PCS models.

 

[Jonathan Edwards]

What on earth is mitochondrial repression?
An abstract with no data and all sorts of value-laden terms is not of interest to me.

 

[InitialConditions]

I believe this is a fake/AI paper. The list of affiliations is highly suspect. None of the author profiles online matches the content of the paper.

 

[Mortal Machinery]

I believe this is a fake/AI paper. The list of affiliations is highly suspect. None of the author profiles online matches the content of the paper.

Not saying anything about the content of the paper. It very well might all be incorrect.

I think however, there might be an issue with the Frontiers profile links that led to the conclusion this is fake, as the authors do appear to be real people with relevant backgrounds (see spoiler below), several of whom have published previous papers together. Many of those papers are related to human biology during space exploration. But there are some previous papers with "mitochondria" in the title, and Guarnieri has two previous Covid related publications.

In this article, they provide a lot of detail about their methods, several data plots and figures, supplemental information, and have made all the data and code used for their analysis available. They also acknowledge the study limitations. That is more than we can say for some papers that get discussed here.

I know nothing about this team or the quality of the work, but it does seem like a genuine effort, and should be evaluated on its actual content.

Spoiler: Data and Code Availability

All data used in this study are publicly available and can be accessed through their respective repository using the accession numbers listed in the “Experimental Model and Subject Details” section below. Code and gene lists utilized in this paper, can be found at https://github.com/easlinger, and https://github.com/shehbeel. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Spoiler: Author Info

Alexia Tasoula - https://www.linkedin.com/in/alexia-tasoula-01819bab https://www.researchgate.net/profile/Alexia-Tasoula https://www.ohio.edu/news/2026/03/2...-universitys-2026-three-minute-thesisr-finals
Shehbeel Arif - https://www.linkedin.com/in/shehbeel/ https://www.researchgate.net/profile/Shehbeel-Arif
Ethan Waisberg - https://www.businessweekly.co.uk/posts/cambridge-eye-screening-tech-brought-to-earth-via-nasa-trials https://www.researchgate.net/profile/Ethan-Waisberg
Lucas Bauer - https://genetics.sciences.ncsu.edu/people/lucas-bauer/
Elizabeth Aslinger - https://www.aslingerconsulting.com/
Joseph Guarnieri - https://bmsis.org/people/ https://www.researchgate.net/profile/Joseph-Guarnieri

 

[Jonathan Edwards]

I know nothing about this team or the quality of the work, but it does seem like a genuine effort, and should be evaluated on its actual content.

OK but the abstract has no meaningful content.

 

[Jonathan Edwards]

And presumably any member of a college of osteopathic medicine is comfortable with fake science.

 

[marshtacky]

And presumably any member of a college of osteopathic medicine is comfortable with fake science.

As far as I understand in the US “osteopathic” is just a historic type of medical school— about 10% of licensed US physicians are DOs rather than MDs. Yes they originated in some 19th century pseudoscience although arguably so did other US medical schools. (let’s be real pretty much all of medicine was pseudo
science in the 19th century when many of these programs started.) the curriculums are identical except the DOs usually get extra training in musculoskeletal stuff I think. anyway I’m not sure it necessarily refers to the “ alternative medicine” trends here, not in the way it does outside of the US. My immunologist at Yale was a DO

 

[ScoutB]

about 10% of licensed US physicians are DOs rather than MDs.

Yes, I read that there has been an explosion in DOs thanks to the artificial cap the US put on MDs in 1997.

 

[Jonathan Edwards]

the curriculums are identical except the DOs usually get extra training in musculoskeletal stuff I think.

As far as i am concerned that is enough of a problem. These are still training schools for 'osteopathic physicians'.

Yes there has always been a lot of pseudoscience in medicine but to apply to a school where that is official seems to me either an admission that you don't think you will get in to a school that tries to move on or an acceptance of continuing that pseudoscience. It would not be difficult to change a name.

 

[Jonathan Edwards]

Yes, I read that there has been an explosion in DOs thanks to the artificial cap the US put on MDs in 1997.

Interesting that that is the time when James LeFanu reckons medical science collapsed (and I agree).

 

[Verity]

As far as i am concerned that is enough of a problem. These are still training schools for 'osteopathic physicians'.

Yes there has always been a lot of pseudoscience in medicine but to apply to a school where that is official seems to me either an admission that you don't think you will get in to a school that tries to move on or an acceptance of continuing that pseudoscience. It would not be difficult to change a name.

Most of the younger DOs don’t buy into it. I’m pretty sure it’s going to die out in not too long. The rest of the training is perfectly fine, and DOs work alongside MDs with no problem. It’s normal to apply broadly to medical schools in the US and just ignore the MSK thing. It’s just a holdover, and everyone knows it.

 

[Jonathan Edwards]

Most of the younger DOs don’t buy into it. I’m pretty sure it’s going to die out in not too long. The rest of the training is perfectly fine, and DOs work alongside MDs with no problem. It’s normal to apply broadly to medical schools in the US and just ignore the MSK thing. It’s just a holdover, and everyone knows it.

Which I guess demonstrates that the whole system is happy to sell its soul to the devil, in order to get a nice dollar income. Sorry, but this makes no sense to me. It is like the shenanigans at FDA. It is why the top class US textbooks of the 1970s have been replaced by inane Twitter/X postings by so-called 'eminent scientists'. Why decent ME/CFS research is still not funded.

When a holdover looks like it has become policy for the indefinite future (and that's if medical science isn't officially abolished in the meantime) I would worry a lot.

 

[marshtacky]

Which I guess demonstrates that the whole system is happy to sell its soul to the devil, in order to get a nice dollar income. Sorry, but this makes no sense to me. It is like the shenanigans at FDA. It is why the top class US textbooks of the 1970s have been replaced by inane Twitter/X postings by so-called 'eminent scientists'. Why decent ME/CFS research is still not funded.

When a holdover looks like it has become policy for the indefinite future (and that's if medical science isn't officially abolished in the meantime) I would worry a lot.

You’re definitely not wrong about that!! it’s a mess. The more I learn the more disappointed I am in our entire medical system.

 

[marshtacky]

The paper said:

Experimental model and subject details​

Overview​

This manuscript integrates data from a diverse set of experimental models spanning animal, tissue, blood-based, and postmortem human studies. Each dataset was originally generated by prior investigators and is described in full detail within the corresponding publications; readers are referred to those citations for comprehensive methodological information (14–16, 20, 22, 42–44).

 

[marshtacky]

The study limitations said:

Similarly, while the Syrian hamster model provides a valuable controlled system for studying post-acute molecular trajectories, nearly 100% of infected hamsters develop PCS-like phenotypes compared to only about 10-26% of humans with PASC/PCS. This suggests that the hamster model may represent an exaggerated post-viral phenotype that fails to capture the heterogeneity, risk factors and incomplete penetrance characteristic of human PASC

I’ve never heard of a hamster model demonstrating long Covid like phenotypes…
Are there any relevant papers that have been discussed on this forum?

The paper said:

Hamster model for the heart, lung, kidney, muscle, and brain tissues​

The Golden Syrian hamster model recapitulates key aspects of human COVID-19, including high viral replication in the respiratory tract, strong systemic interferon responses, and organ-specific inflammatory signatures that persist into chronic stages (15, 20). Longitudinal studies have demonstrated that SARS-CoV-2-infected hamsters develop sustained, multi-organ transcriptional and inflammatory alterations after recovery that parallel molecular features observed in humans following acute infection. In the present study, we leverage this validated model to examine post-acute immunometabolic remodeling across tissues. While hamsters do not model the full heterogeneity of PCS as defined in humans, they provide a mechanistically tractable system for investigating persistent molecular consequences of SARS-CoV-2 infection.

For the hamster tissues analyzed in this study, 6- to 7-week-old male Golden Syrian hamsters (Mesocricetus auratus) were obtained from Charles River Laboratories and acclimated in a CDC/USDA-approved BSL-3 facility for at least 7 days prior to infection. Animals were intranasally inoculated under ketamine/xylazine anesthesia with either phosphate-buffered saline (mock) or SARS-CoV-2 USA-WA1/2020 (1×103 PFU in 100 μL). Hamsters were euthanized at 3, 31, and—specifically for skeletal muscle analyses—61dpi. Following PBS perfusion, lung, heart, kidney, quadriceps muscle, and multiple brain regions—including the olfactory bulb, medial prefrontal cortex, striatum, thalamus, cerebellum, and trigeminal ganglion—were harvested. Tissues designated for viral quantification and transcriptomic analyses were homogenized in PBS or TRIzol. Infectious viral titers in lung tissue were quantified via plaque assay on Vero-E6 cells, while SARS-CoV-2 RNA, including subgenomic N, was measured by qRT-PCR (15, 20).

In addition to transcriptomic analyses, behavioral and biochemical assays were performed on the infected hamsters. Notably, histology-associated inflammation was observed in the lungs and kidneys, along with behavioral and molecular changes consistent with SARS-CoV-2–related brain dysfunction (20). Furthermore, quadriceps muscle displayed signatures of structural, inflammatory, and microvascular alterations, including capillary remodeling, macrophage infiltration, interferon-driven responses, and complement activation (15).

 

[Mortal Machinery]

It appears that the first author is a PhD student, not a DO.
The second has an MS in bioinformatics from Johns Hopkins and is completing an MD at Drexel.
Aslinger is a PhD (Purdue) and appears to have mostly contributed the statistical consulting.
Guarnieri is a PhD (Drexel) - Molecular Biology, Biochemistry, Virology, Mitochondria (per his CV on LinkedIn)

It's fine if folks think the paper has no substance and is not worth the time or effort. But dismissing based on the authors' credentials seems uncalled for.

 

[SNT Gatchaman]

Some of the senior author's previous papers —

Respiratory viral infections awaken metastatic breast cancer cells in lungs (2025, Nature)

Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes (2024, Proceedings of the National Academy of Sciences)

SARS-CoV-2 Mitochondrial Metabolic and Epigenomic Reprogramming in COVID-19 (2024, Pharmacological Research)

Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts (2023, Science Translational Medicine)

 

[ScoutB]

I’ve never heard of a hamster model demonstrating long Covid like phenotypes

Don’t know about long Covid, but I’ve heard the (Syrian) hamster is used a lot for acute covid research because apparently their ace2 receptors are similar to human ace2 (and so susceptible to Covid). Vs lab mice are more Covid resistant IIRC.

 

[Jonathan Edwards]

But dismissing based on the authors' credentials seems uncalled for.

We are constantly bombarded with hype about researchers' credentials and I suspect people with ME/CFS often put a lot of store by that. I think it is legitimate to redress the balance a bit and point out just how rubbish most research is these days and that 'star' researchers are often those who churn out year on year the same inconclusive stuff about tired ideas that should have been put to bed long ago.

Nobody should put their name to an abstract like this.

 

[InitialConditions]

Not saying anything about the content of the paper. It very well might all be incorrect.

I think however, there might be an issue with the Frontiers profile links that led to the conclusion this is fake, as the authors do appear to be real people with relevant backgrounds (see spoiler below), several of whom have published previous papers together. Many of those papers are related to human biology during space exploration. But there are some previous papers with "mitochondria" in the title, and Guarnieri has two previous Covid related publications.

In this article, they provide a lot of detail about their methods, several data plots and figures, supplemental information, and have made all the data and code used for their analysis available. They also acknowledge the study limitations. That is more than we can say for some papers that get discussed here.

I know nothing about this team or the quality of the work, but it does seem like a genuine effort, and should be evaluated on its actual content.

Spoiler: Data and Code Availability

All data used in this study are publicly available and can be accessed through their respective repository using the accession numbers listed in the “Experimental Model and Subject Details” section below. Code and gene lists utilized in this paper, can be found at https://github.com/easlinger, and https://github.com/shehbeel. Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Spoiler: Author Info

Alexia Tasoula - https://www.linkedin.com/in/alexia-tasoula-01819bab https://www.researchgate.net/profile/Alexia-Tasoula https://www.ohio.edu/news/2026/03/2...-universitys-2026-three-minute-thesisr-finals
Shehbeel Arif - https://www.linkedin.com/in/shehbeel/ https://www.researchgate.net/profile/Shehbeel-Arif
Ethan Waisberg - https://www.businessweekly.co.uk/posts/cambridge-eye-screening-tech-brought-to-earth-via-nasa-trials https://www.researchgate.net/profile/Ethan-Waisberg
Lucas Bauer - https://genetics.sciences.ncsu.edu/people/lucas-bauer/
Elizabeth Aslinger - https://www.aslingerconsulting.com/
Joseph Guarnieri - https://bmsis.org/people/ https://www.researchgate.net/profile/Joseph-Guarnieri

Ok. I shouldn't have posted last night without explaining why the paper struck me as potentially problematic. It was getting late and I needed to come off the laptop.

I have many questions and would not claim that this paper was potentially not authentic without first doing a bit of digging (which is how I spent part of my Friday evening). But perhaps I should have expressed my doubts in less bombastic terms.

Some peculiarities
1) I visited most of those links linked above. This is a really bizarre collection of authors. For most, I could not find the usual academic (university-hosted homepage) that you'd expect. A ResearchGate or Google Scholar profile is not enough to prove legitimacy. They can be easily faked and populated with sham/AI papers giving huge citation scores.

Most seem like recent graduates working in very different fields. Several work for Guarnieri Research Group LLC (registered in Philadelphia), named after the senior author here, although he also seems to also work for Blue Marble Space Institute in Seattle.

Take Ethan Waisberg. His affiliation is given as Cambridge, but he does not have a Cambridge homepage. However, it looks like he's part doctor/part academic, so that may explain that. Why is a neuro-opthalmologist with an interest in the effects of space flight doing multi-omics of long covid? He's supposed to be busy developing an astronaut vision testing system and startup called AngioGenius: https://www.ucd.ie/medicine/news/2026/drethanwaisberglaunchesastronautvisiontestingsystem/

Lucas Bauer is a PhD or post-doc at NC State but seems to use cameras to study plants: https://datascienceacademy.ncsu.edu/nc-state-student-researcher-stories/#:~:text=they make mistakes.-,Lucas Bauer,-Bio: Lucas

Elizabeth Aslinger, one of the corresponding authors, has a background in psychology and now has her own scientific consultancy firm. But, as corresponding author on this paper, she has provided a Yale alumni email address instead of her business email address. She was at Yale a decade ago as a student. How strange. Why?



2) Have they provided their data and code? I'm not so sure. They've just linked to two of their Github profiles. Where are the 'code and gene lists', or any of the actual code for this project/publication? This was a red flag for me, but perhaps it's just bad practice.

3) There's no data or methods section, which I found strange, but this could be explained by their claiming to pull together different datasets from prior investigations.

4) There's absolutely no funding for this work, but in the Author contributions section, Elizabeth Aslinger is listed as responsible for 'Funding acquisition'.



5) Figures S2–S4 are blank for me in the supplementary .docx file. Perhaps someone can try and open this in Word and see if they are blank? I don't have Word so it may be just a problem at my end.