Role of the Complement System and Vascular Endothelium in COVID-19 Pathogenesis
Notice bibliographique
Résumé
Background: Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 infection has become a global pandemic, presenting with varying degrees of severity from respiratory distress to multi-organ damage. Kidneys are of several organs affected in COVID-19, with acute kidney injury (AKI) being a common consequence, occurring in more than 30% of patients with severe COVID-19. While the underlying mechanisms of COVID-19 pathogenesis remain poorly understood, there is evidence linking complement system overactivation and endothelial injury to organ damage that increases the risk of mortality in COVID-19. Evidence from previous coronavirus epidemics also suggest direct involvement of inflammation, complement dysregulation, and endothelial cell dysfunction. Thus, we hypothesize that vascular endothelial injury resulting from complement overactivation contributes to COVID-19-associated organ injury. Methods: Clinical information and sera from SARS-CoV-2+ patients with mild (n=7) and severe COVID-19 (n=7) diseases were obtained from the Canadian COVID-19 Prospective Cohort Study (CANCOV). Complement activation on ECs was evaluated via immunofluorescence assays, measuring the deposition of complement products C3b and C5b-9 on Human Umbilical Vein Endothelial Cells exposed to control or patient sera. In addition, a permeability assay using a transwell model was used to measure the integrity of the endothelial monolayer exposed to patient sera. Results: Complement was found to be overactivated on ECs treated with SARS-CoV-2+ patient sera compared to those treated with normal human serum as evidenced by significantly increased C3b and C5b-9 deposition. While ECs treated with sera from patients with mild COVID-19 seemed to have higher C3b deposition, ECs treated with sera from patients with severe COVID-19 disease were associated with higher C5b-9 deposition. In addition, increased permeability of the monolayer incubated with SARS-CoV-2+ patient sera was seen over time regardless of disease severity. However, ECs tretaed with severe COVID-19 patient sera had signficiantly increased vascular leakiness as evidenced by increased permeability of the treated monolayer. Conclusions: Thus, we conclude that complement is overactivated in SARS-CoV-2+ patients and use of anti-complement therapies may be an effective strategy in treating COVID-19 associated vascular injury, hyperinflammation, and organ damage.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,000 |
| 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 | 0,000 |
| 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 découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».