Safety of baricitinib in vaccinated patients with severe and critical COVID-19 sub study of the randomised Bari-SolidAct trial.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Viermyr Hans-Kittil, Tonby Kristian, Ponzi Erica, Trouillet-Assant Sophie, Poissy Julien, Arribas José R, Dyon-Tafani Virginie, Bouscambert-Duchamp Maude, Assoumou Lambert, Halvorsen Bente, Tekin Nuriye Basdag, Diallo Alpha, De Gastines Lucie, Munthe Ludvig A, Murphy Sarah Louise, Ueland Thor, Michelsen Annika E, Lund-Johansen Fridtjof, Aukrust Pål, Mootien Joy, Dervieux Benjamin, Zerbib Yoann, Richard Jean-Christophe, Prével Renaud, Malvy Denis, Timsit Jean-François, Peiffer-Smadja Nathan, Roux Damien, Piroth Lionel, Ait-Oufella Hafid, Vieira Cesar, Dalgard Olav, Heggelund Lars, Müller Karl Erik, Møller Jannicke Horjen, Kildal Anders Benjamin, Skogen Vegard, Aballi Saad, Sjøberg Øgaard Jonas Daniel, Dyrhol-Riise Anne Ma, Tveita Anders, Alirezaylavasani Amin, Costagliola Dominique, Yazdanpanah Yazdan, Olsen Inge Christoffer, Dahl Tuva Børresdatter, Kared Hassen, Holten Aleksander Rygh, Trøseid Marius
Аннотация
METHODS: Biobanked samples from 146 participants (55 vaccinated vs. 91 unvaccinated) were analysed longitudinally for inflammation markers, humoral responses, tissue viral loads, and plasma viral antigens on days 1, 3, and 8. High-dimensional analyses, including RNA sequencing and flow cytometry, were performed on available samples. Mediation analyses were used to assess relationships between SAEs, baseline-adjusted biomarkers, and treatment-vaccination status.
FINDINGS: Vaccinated participants were older, more frequently hospitalized, had more comorbidities, and exhibited higher nasopharyngeal viral loads. Baricitinib treatment did not affect antibody responses or viral clearance, but reduced markers of T-cell and monocyte activation compared to placebo (sCD25, sCD14, sCD163, sTIM-3). Age, baseline levels of plasma viral antigen, and several inflammatory markers, as well as IL-2, IL-6, Neopterin, CXCL16, sCD14, and suPAR on day 8 were associated with the occurrence of SAEs. However, mediation analyses of markers linked to SAEs, baricitinib treatment, or vaccination status did not reveal statistically significant interactions between vaccination status and SAEs.
INTERPRETATION: This sub-study did not identify any virus- or host-related biomarkers significantly associated with the interaction between SARS-CoV-2 vaccination status and the safety of baricitinib. However, caution should be exercised due to the moderate sample size.
FUNDING: EU Horizon 2020 (grant number 101015736).