Novel biomarkers of mitochondrial dysfunction in Long COVID patients, 2024, Szögi et al.

Novel biomarkers of mitochondrial dysfunction in Long COVID patients
Szögi, Titanilla; Borsos, Barbara N.; Masic, Dejana; Radics, Bence; Bella, Zsolt; Bánfi, Andrea; Ördög, Nóra; Zsiros, Csenge; Kiricsi, Ágnes; Pankotai-Bodó, Gabriella; Kovács, Ágnes; Paróczai, Dóra; Botkáné, Andrea Lugosi; Kajtár, Béla; Sükösd, Farkas; Lehoczki, Andrea; Polgár, Tamás; Letoha, Annamária; Pankotai, Tibor; Tiszlavicz, László

Coronavirus disease 2019 (COVID-19) can lead to severe acute respiratory syndrome, and while most individuals recover within weeks, approximately 30–40% experience persistent symptoms collectively known as Long COVID, post-COVID-19 syndrome, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). These enduring symptoms, including fatigue, respiratory difficulties, body pain, short-term memory loss, concentration issues, and sleep disturbances, can persist for months. According to recent studies, SARS-CoV-2 infection causes prolonged disruptions in mitochondrial function, significantly altering cellular energy metabolism.

Our research employed transmission electron microscopy to reveal distinct mitochondrial structural abnormalities in Long COVID patients, notably including significant swelling, disrupted cristae, and an overall irregular morphology, which collectively indicates severe mitochondrial distress. We noted increased levels of superoxide dismutase 1 which signals oxidative stress and elevated autophagy-related 4B cysteine peptidase levels, indicating disruptions in mitophagy. Importantly, our analysis also identified reduced levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) in these patients, serving as a novel biomarker for the condition.

These findings underscore the crucial role of persistent mitochondrial dysfunction in the pathogenesis of Long COVID. Further exploration of the cellular and molecular mechanisms underlying post-viral mitochondrial dysfunction is critical, particularly to understand the roles of autoimmune reactions and the reactivation of latent viruses in perpetuating these conditions. This comprehensive understanding could pave the way for targeted therapeutic interventions designed to alleviate the chronic impacts of Long COVID. By utilizing circulating ccf-mtDNA and other novel mitochondrial biomarkers, we can enhance our diagnostic capabilities and improve the management of this complex syndrome.

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A team from Hungary:
Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary

Their hypothesis:

They looked at:

• nasal and bronchial samples - mitochondria visualised with transmission electron microscopy
• levels of proteins crucial to mitochondrial dynamics—specifically autophagy-related 4B cysteine peptidase (ATG4B), mitofusin 2 (MFN2), and dynamin-related protein 1 (DRP1)
• superoxide dismutase 1 (SOD1) protein levels - to assess oxidative stress status
• circulating cell-free mitochondrial DNA (ccf-mtDNA) in blood plasma to evaluate the integrity and functionality of mitochondrial recycling processes

 

Electron microscopy of mitochondria

So:

• small numbers of samples,
• controls not well matched (very different ages, and the controls aren't healthy controls,
• post-Covid symptoms of the Long Covid group are primarily olfactory problems, so not very relevant to ME/CFS

Unfortunately, I think all those problems add up to any findings not being very helpful, at least from our perspective.