Passive immunotherapy for adults hospitalized with COVID-19: An individual participant data meta-analysis of six randomized controlled trials
Notice bibliographique
Résumé
BACKGROUND: Anti-SARS-CoV-2 monoclonal antibodies (mAb) reduce the risk of hospitalization in outpatients with mild-to-moderate COVID-19. However, the efficacy of treatment with mAbs and other passive immunotherapies in patients hospitalized with severe COVID-19 is not clear. The objective of this study was to assess the clinical effect of passive immunotherapy and its heterogeneity according to baseline endogenous neutralizing antibody status and SARS-CoV-2 antigen level, in adults hospitalized with SARS-CoV-2 infection and severe COVID-19. METHODS AND FINDINGS: We carried out a two-stage individual participant data meta-analysis of six double-blind, randomized, placebo-controlled trials conducted under the Therapeutics for Inpatients with COVID-19 (TICO) and the similarly designed Inpatient Treatment with Anti-Coronavirus Immunoglobulin (ITAC) master protocols. Within each trial, three major outcomes (sustained recovery, mortality, and a composite safety outcome) were compared between treatment and placebo using Fine-Gray and Cox proportional hazards models. Trial-specific treatment differences for each of the three outcomes were pooled using a common effect meta-analysis. A total of 3,079 patients hospitalized for COVID-19 were enrolled in the six trials. Only 18% had received at least one dose of an anti-SARS-CoV-2 vaccine. Overall, the median plasma SARS-CoV-2 antigen level was 1,421 (IQR: 231-4,568) pg/mL, and 51% of patients were endogenous neutralizing antibody positive at study entry. The overall summary estimate of sustained recovery rate ratio (RRR) of the treatment versus placebo group was 1.06 (95% CI [0.99,1.14]), but this varied significantly by antibody serostatus. The RRR was 1.16 (95% CI [1.04,1.29]) among seronegative patients and 0.97 (95% CI [0.88,1.07]) in seropositive patients [p = 0.02 for interaction (the difference in RRR between seropositive and seronegative patients)]. The summary hazard ratio (HR) for mortality comparing treatment to placebo was 0.81 (95% CI [0.64,1.03]) overall, 0.69 (95% CI [0.50,0.95]) in seronegative patients, and 0.96 (95% CI [0.66,1.39]) in seropositive patients (interaction p = 0.18). There was no evidence that the treatment effect on any outcome differed according to antigen level, whether overall or within serostatus subgroups. In regards to the composite safety outcome, the overall summary HR comparing treatment group to placebo was 0.89 (95% CI [0.66,1.21]; Q = 3.47 [p = 0.63], I2 = 0.0%), and it was 0.83 (95% CI [0.70,0.99]) and 1.04 (95% CI [0.86,1.26]) in seronegative and seropositive patients, respectively. The main limitation of the methodology is that these results are limited to the analysis of the six trials in ACTIV-3/TICO and ITAC and are not intended to be a complete summary of all trials of passive immunotherapy. CONCLUSIONS: Passive immunotherapy might be a useful treatment option for hospitalized patients with COVID-19 if administered before the appearance of endogenous antibodies. Development of similar passive immunotherapy could also be especially important during the early stages of a viral pandemic, or as novel viral variants emerge.
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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 | 0,026 | 0,136 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,077 | 0,009 |
| Bibliométrie | 0,003 | 0,003 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,002 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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; les deux têtes enseignantes s’accordent sur ce qui est montré ici.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».