Mitochondria and cytochrome components released into the plasma of severe COVID-19 and ICU acute respiratory distress syndrome patients
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Résumé
Abstract Introduction Proteomic analysis of human plasma by LC–ESI–MS/MS has discovered a limited number of new cellular protein biomarkers that may be confirmed by independent biochemical methods. Analysis of COVID-19 plasma has indicated the re-purposing of known biomarkers that might be used as prognostic markers of COVID-19 infection. However, multiple molecular approaches have previously indicated that the SARS-COV2 infection cycle is linked to the biology of mitochondria and that the response to infections may involve the action of heme containing oxidative enzymes. Methods Human plasma from COVID-19 and ICU-ARDS was analyzed by classical analytical biochemistry techniques and classical frequency-based statistical approaches to look for prognostic markers of severe COVID-19 lung damage. Plasma proteins from COVID-19 and ICU-ARDS were identified and enumerated versus the controls of normal human plasma (NHP) by LC–ESI–MS/MS. The observation frequency of proteins detected in COVID-19 and ICU-ARDS patients were compared to normal human plasma, alongside random and noise MS/MS spectra controls, using the Chi Square (χ 2 ) distribution. Results PCR showed the presence of MT-ND1 DNA in the plasma of COVID-19, ICU-ARDS, as well as normal human plasma. Mitochondrial proteins such as MRPL, L2HGDH, ATP, CYB, CYTB, CYP, NDUF and others, were increased in COVID-19 and ICU-ARDS plasma. The apparent activity of the cytochrome components were tested alongside NHP by dot blotting on PVDF against a purified cytochrome c standard preparation for H 2 O 2 dependent reaction with luminol as measured by enhanced chemiluminescence (ECL) that showed increased activity in COVID-19 and ICU-ARDS patients. Discussion The results from PCR, LC–ESI–MS/MS of tryptic peptides, and cytochrome ECL assays confirmed that mitochondrial components were present in the plasma, in agreement with the established central role of the mitochondria in SARS-COV-2 biology. The cytochrome activity assay showed that there was the equivalent of at least nanogram amounts of cytochrome(s) in the plasma sample that should be clearly detectable by LC–ESI–MS/MS. The release of the luminol oxidase activity from cells into plasma forms the basis of a simple and rapid test for the severity of cell damage and lung injury in COVID-19 infection and ICU-ARDS. Graphical Abstract
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Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découle