Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach

Abstract:

Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood. Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40).

Untargeted metabolomic analysis using CE-ESI(+/-)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/-)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients.

We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.

Source: Martínez S, Albóniga OE, López-Huertas MR, Gradillas A, Barbas C. Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach. J Proteome Res. 2024 Apr 2. doi: 10.1021/acs.jproteome.3c00706. Epub ahead of print. PMID: 38566450. https://pubmed.ncbi.nlm.nih.gov/38566450/

Hyperventilation and chronic fatigue syndrome

Abstract:

We studied the link between chronic fatigue syndrome (CFS) and hyperventilation in 31 consecutive attenders at a chronic fatigue clinic (19 females, 12 males) who fulfilled criteria for CFS based on both Oxford and Joint CDC/NIH criteria. All experienced profound fatigue and fatigability associated with minimal exertion, in 66% developing after an infective episode. Alternative causes of fatigue were excluded.

Hyperventilation was studied during a 43-min protocol in which end-tidal PCO2 (PETCO2) was measured non-invasively by capnograph or mass spectrometer via a fine catheter taped in a nostril at rest, during and after exercise (10-50 W) and for 10 min during recovery from voluntary overbreathing to approximately 2.7 kPa (20 mmHg). PETCO2 < 4 kPa (30 mmHg) at rest, during or after exercise, or at 5 min after the end of voluntary overbreathing, suggested either hyperventilation or a tendency to hyperventilate. Most patients were able voluntarily to overbreathe, but not all were able to exercise.

Twenty-two patients (71%) had no evidence of hyperventilation during any aspect of the test. Only four patients had unequivocal hyperventilation, in one associated with asthma and in three with panic. Only one patient with severe functional disability and agoraphobia had hyperventilation with no other obvious cause. A further five patients had borderline hyperventilation, in which PETCO2 was < 4 kPa (30 mmHg) for no more than 2 min, when we would have expected it to be normal. There was no association between level of functional impairment and degree of hyperventilation. There is only a weak association between hyperventilation and chronic fatigue syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Comment in: Hyperventilation and the chronic fatigue syndrome. [Q J Med. 1994]

Source: Saisch SG, Deale A, Gardner WN, Wessely S. Hyperventilation and chronic fatigue syndrome. Q J Med. 1994 Jan;87(1):63-7. http://www.ncbi.nlm.nih.gov/pubmed/8140219