Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies:a report from the EPICOVIDEHA registry

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).</p

Nirmatrelvir/ritonavir in COVID-19 patients with haematological malignancies: a report from the EPICOVIDEHA registry

Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan-Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448-4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619-8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093-0.732) and obesity (aOR 0.105, 95%CI 0.014-0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p&nbsp;=&nbsp;0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS.

peer reviewedAllogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2-4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32-1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28-1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome

Decoding the historical tale: COVID-19 impact on haematological malignancy patients-EPICOVIDEHA insights from 2020 to 2022

The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced.Peer reviewe

Evangelical protestantism and conservative mobilizations in Taiwan, Hong Kong and China

À partir d'une enquête multi-située (Taipei, Hong Kong, Shenzhen et Pékin, 2017-2019), cette recherche analyse les mobilisations conservatrices des évangéliques sinophones taïwanais et hongkongais dans le monde sinophone. Depuis les années 1980, dans le contexte de la politique de réforme et d'ouverture en Chine et de la démocratisation de Taïwan, le protestantisme évangélique est en pleine expansion au sein de ces territoires. Les élites sinophones occupent un rôle d'intermédiaires dans cette diffusion les conduisant à adhérer à la fois à des doctrines émanant de la Droite chrétienne telles que les valeurs familiales traditionnelles, la critique de la persécution religieuse en Chine ou le libre-échange mais aussi à forger des alliances avec le Front uni (stratégie politique et réseau de groupes rattaché au Parti communiste chinois). En posant la question de leur rôle dans la propagation d'idéaux conservateurs au sein d'un contexte géopolitique marqué par des logiques nationalistes rivales, cette thèse montre que le militantisme évangélique est dès lors moins lié à l'ancienne "éthique protestante" qu'à de nouvelles normes d'engagement qui articulent néolibéralisme, conservatisme politique et fondamentalisme religieux. Néanmoins, d'autres groupes protestants, développant des relations complexes avec les réseaux évangéliques, s'impliquent dans le développement d'un idéal protestant de la société civile ou réinventent les normes chrétiennes de genre et de sexualité. En analysant les dissensions profondes qu'a creusé l'évangélisme dans le sillage de sa propagation, cette thèse contribue à la littérature récente réarticulant expérience religieuse et mobilisations politiques.Based on a multi-sited ethnographic fieldwork (Taipei, Hong Kong, Shenzhen and Beijing, 2017-2019), this doctoral thesis discusses the conservative mobilizations of the sinophone evangelical elites from Hong Kong and Taiwan. Since the 1980s, with the politics of reforms and opening up in China and the democratization of Taiwan, evangelical protestantism has rapidly expanded in these territories. The sinophone elites are major brokers in this expansion, which has led them to embrace doctrines related to the Christian Right such as traditional family values, an opposition to the religious persecution in China or the free-market but also to forge alliances with the United front (a political tactic and an alliance of groups supervised by the Chinese communist party). By addressing the question of their role in the spread of conservative ideas in a geopolitical context defined by rival nationalist logics, this thesis shows that evangelical activism is less related to a generic "protestant ethic" than to new forms of commitment that articulate neoliberalism, conservatism and fundamentalism. However, other protestant groups have established complex relationships with the evangelical networks. Some groups promote a protestant ideal of civil society while others reinvent Christian norms on gender and sexuality. By analyzing the divisions that evangelicalism has carved in the path of its expansion, this thesis seeks to contribute to the recent literature articulating religious experience and political mobilizations

La sinisation du protestantisme en Chine

Le plan quinquennal pour la sinisation du protestantisme (2018-2022) a été publié en Chine le 27 mars 2018 sur le site des deux comités, organes du gouvernement chargés de l’encadrement du protestantisme. La sinisation est un mot d’ordre propagé par les instances chrétiennes chinoises depuis 2013 dans le but de construire une « Eglise fidèle à la vérité de la Bible enracinée dans la culture chinoise». Ce discours est associé à la mise en œuvre d’une politique d’endiguement à l’égard des groupes religieux « occidentaux », qui sont perçus par les autorités comme une menace à la stabilité sociale du pays. Les églises constitueraient en effet un réseau favorable à la dissémination d’idées démocratiques, le christianisme ayant de fait historiquement contribué à la chute de régimes autoritaires dans les cas de la Pologne ou de l’Afrique du sud

La visibilité des organisations protestantes en Chine sous le regard de l’État-parti

Fondé sur des enquêtes de terrain effectuées dans plusieurs villes (Pékin, Shenzhen et Changsha), l’article analyse les stratégies de visibilité des organisations protestantes chinoises. Dans un contexte où l’État-parti cherche souvent à effacer toute trace du protestantisme au sein de l’espace public, les Églises – enregistrées auprès des autorités ou souterraines – mettent elles-mêmes en scène leur disparition en proclamant leur adhésion au discours officiel. Cette allégeance de façade les conduit à sécuriser leurs activités religieuses qui se déplacent ainsi dans des sphères peu visibles, communautaires ou privées. L’analyse porte d’abord sur la visibilité de l’État dans l’espace protestant, puis, dans les deux parties suivantes, sur l’adaptation des Églises aux restrictions politiques et leurs réactions face au durcissement des directives religieuses de 2017.This article analyzes the different tactics of visibility used by protestant organizations in China, on fieldworks carried in several cities (Beijing, Shenzhen and Changsha). In a context where the Party-State often aims at erasing Protestantism from the public sphere, registered or underground churches most of the time stage their disappearance from the public sphere. By proclaiming their allegiance to the official transcript, these congregations secure their religious activities, which are relocated to the non-visible private and communitarian realms. This article first examines the overarching presence of the State in the protestant sphere; and then focuses on the adaptation of churches to these political constraints and their reactions to the new 2017 religious regulations

Développement de méthodes combinatoires pour la découverte de ligands à base de cyclopeptides.

Combinatorial chemistry represents an efficient strategy to discover new bioactives molecules. In this context, we investigated two combinatorial approaches to prepare libraries of cyclopeptide-based ligands. First, we developed a randomized chemoselective assembly of biomolecules onto peptidic template. We thus obtained in solution libraries of heteroglycoclusters that were screened by affinity chromatography with immobilized Concanavalin A as model lectin. In a second approach, libraries of cyclic peptides have been prepared on solid support by split and mix method. These libraries have been designed following the decoding algorithm developed by Reymond's group (Bern, Switzerland) which allows the sequence determination of each peptide. The screening with vitamin B12 and Casein Kinase 2 have been realizedLa chimie combinatoire est un moyen efficace pour découvrir des molécules biologiquement actives. Dans ce travail, nous avons exploré deux approches combinatoires différentes pour synthétiser des bibliothèques de cyclopeptides. Tout d'abord, nous avons développé une stratégie basée sur l'assemblage aléatoire et chimiosélectif de biomolécules sur un châssis peptidique. Cette approche réalisée en solution a permis de générer des bibliothèques d'hétéroglycoclusters et de sélectionner les meilleurs ligands par colonne d'affinité portant une lectine modèle, la Concanavaline A. Dans une seconde approche, des bibliothèques de peptides cycliques ont été préparées par la méthode split and mix. Celles-ci ont été conçues et décodées selon l'algorithme mis au point dans le groupe du Pr. Reymond (Berne, Suisse) qui permet d'attribuer la séquence de chaque peptide sans marquage et de manière quasi-unique. Ces bibliothèques ont été criblées sur le support avec la vitamine B12 et la Caseine Kinase 2

Une œuvre d’intérêt national : la loi du 3 décembre 1966 d’orientation et de programme sur la formation professionnelle

Dans un livre qui relate ses entretiens avec le général de Gaulle, Michel Debré retrace celui du 28 janvier 1966, c’est-à-dire moins de trois semaines après sa nomination comme ministre de l’Économie et des Finances. Le résumé de cet entretien et le commentaire qui l’introduit sont riches d’enseignements en ce qui concerne le sujet dont je dois vous parler : la loi du 3 décembre 1966 sur la formation professionnelle. Ils montrent en effet, s’agissant de la conception même de l’économie, l’éta..