ACE-2-like enzymatic activity in COVID-19 convalescents with persistent pulmonary symptoms associated with immunoglobulin
Notice bibliographique
Résumé
Many difficult-to-understand clinical features characterize COVID-19 and post-acute sequelae of COVID-19 (PASC or long COVID [LC]). These can include blood pressure instability, hyperinflammation, coagulopathies, and neuropsychiatric complaints. The pathogenesis of these features remains unclear. The SARS-CoV-2 Spike protein receptor-binding domain (RBD) binds angiotensin converting enzyme 2 (ACE2) on the surface of host cells to initiate infection. We hypothesized that some people convalescing from COVID-19 may produce anti-RBD antibodies that resemble ACE2 sufficiently to have ACE2-like catalytic activity, that is, they are ACE2-like proteolytic abzymes that may help mediate the pathogenesis of COVID-19 and LC. In previous work, we showed that some people with acute COVID-19 had immunoglobulin-associated ACE2-like proteolytic activity, suggesting that some people with COVID-19 indeed produced ACE2-like abzymes. However, it remained unknown whether ACE2-like abzymes were seen only in acute COVID-19 or whether ACE2-like abzymes could also be identified in people convalescing from COVID-19. Here, we show that some people convalescing from COVID-19 attending a clinic for people with persistent pulmonary symptoms also have ACE2-like abzymes and that the presence of ACE2-like catalytic activity correlates with alterations in blood pressure in an exercise test. IMPORTANCE: Patients who have had COVID-19 can sometimes have troublesome symptoms, termed post-acute sequelae of COVID-19 (PASC) or long COVID (LC), which can include problems with blood pressure regulation, gastrointestinal problems, inflammation, blood clotting, and symptoms like "brain fog." The proximate causes for these problems are not known, which makes these problems difficult to treat definitively. We previously found that some acute COVID-19 patients make antibodies against SARS-CoV-2, the virus that causes COVID-19, that act like an enzyme, angiotensin converting enzyme 2 (ACE2). ACE2 normally helps regulate blood pressure and serves as the receptor for SARS-CoV-2 in the body. We show that patients convalescing from COVID-19 also make antibodies that act like ACE2 and that the presence of those antibodies correlates with problems in blood pressure regulation. The findings provide a new opening to potentially understanding the causes of LC, and so provide direction for the development of new treatments.
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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 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| 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 ».