Biomarkers Associated With Severe COVID-19 Among Populations With High Cardiometabolic Risk
Notice bibliographique
Résumé
Importance: Cardiometabolic parameters are established risk factors for COVID-19 severity. The identification of causal or protective biomarkers for COVID-19 severity may facilitate the development of novel therapies. Objective: To identify protein biomarkers that promote or reduce COVID-19 severity and that mediate the association of cardiometabolic risk factors with COVID-19 severity. Design, Setting, and Participants: This genetic association study using 2-sample mendelian randomization (MR) was conducted in 2022 to investigate associations among cardiometabolic risk factors, circulating biomarkers, and COVID-19 hospitalization. Inputs for MR included genetic and proteomic data from 4147 participants with dysglycemia and cardiovascular risk factors collected through the Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Genome-wide association study summary statistics were obtained from (1) 3 additional independent plasma proteome studies, (2) genetic consortia for selected cardiometabolic risk factors (including body mass index [BMI], type 2 diabetes, type 1 diabetes, and systolic blood pressure; all n >10 000), and (3) the COVID-19 Host Genetics Initiative (n = 5773 hospitalized and 15 497 nonhospitalized case participants with COVID-19). Data analysis was performed in July 2022. Exposures: Genetically determined concentrations of 235 circulating proteins assayed with a multiplex biomarker panel from the ORIGIN trial for the initial analysis. Main Outcomes and Measures: Hospitalization status of individuals from the COVID-19 Host Genetics Initiative with a positive COVID-19 test result. Results: Among 235 biomarkers tested in samples totaling 22 101 individuals, MR analysis showed that higher kidney injury molecule-1 (KIM-1) levels reduced the likelihood of COVID-19 hospitalization (odds ratio [OR] per SD increase in KIM-1 levels, 0.86 [95% CI, 0.79-0.93]). A meta-analysis validated the protective association with no observed directional pleiotropy (OR per SD increase in KIM-1 levels, 0.91 [95% CI, 0.88-0.95]). Of the cardiometabolic risk factors studied, only BMI was associated with KIM-1 levels (0.17 SD increase in biomarker level per 1 kg/m2 [95% CI, 0.08-0.26]) and COVID-19 hospitalization (OR per 1-SD biomarker level, 1.33 [95% CI, 1.18-1.50]). Multivariable MR analysis also revealed that KIM-1 partially mitigated the association of BMI with COVID-19 hospitalization, reducing it by 10 percentage points (OR adjusted for KIM-1 level per 1 kg/m2, 1.23 [95% CI, 1.06-1.43]). Conclusions and Relevance: In this genetic association study, KIM-1 was identified as a potential mitigator of COVID-19 severity, possibly attenuating the increased risk of COVID-19 hospitalization among individuals with high BMI. Further studies are required to better understand the underlying biological mechanisms.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
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 | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,004 | 0,001 |
| Bibliométrie | 0,001 | 0,006 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| 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 ».