Introduction En 2026, l'essentiel de la problématique liée à la COVID-19 concerne les patients immunodéprimés qui peuvent présenter des COVID-19 persistantes (pCOVID-19), caractérisées par un défaut de clairance virale. Les pCOVID-19 peuvent être à l'origine d'émergence de variants préoccupants et de résistance aux antiviraux. C'est pourquoi, la société israélienne de maladies infectieuses a récemment proposé de traiter les pCOVID-19 par trithérapie associant deux antiviraux d'action directe à une immunisation passive. Pourtant, peu d'études évaluent l'efficacité clinique de ces associations. Matériels et méthodes Etude de cohorte rétrospective multicentrique française incluant des patients immunodéprimés avec une infection persistante (>14 jours) par le SARS-CoV-2 prouvée par PCR, hospitalisés en service de médecine et oxygénorequérant (échelle OMS de sévérité = 5), pour lesquels un traitement par PCC seul ou en association concomitante à une thérapeutique antivirale d'action directe a été initiée entre le 1er janvier 2023 et le 1er juin 2025. Le critère de jugement principal était l'échec à J28 de l'initiation du PCC. Ce critère composite était défini par une PCR SARS-CoV-2 positive, et/ou la nécessité d'une nouvelle ligne thérapeutique antivirale ou immunomodulatrice, et/ou le décès à J28. Résultats Nous avons inclus 64 patients immunodéprimés qui présentaient une pCOVID-19. L'âge médian était de 70 ans IQR (63-76), 36 (56,2%) étaient des hommes. Le terrain d'immunosuppression le plus fréquent était le lymphome (n=38; 59,4%) et le traitement immunosuppresseur le plus fréquemment utilisé était un anti-CD20 (n=35; 54,7%). La dexaméthasone était administrée dans 54,7% des cas. Les patients traités par monothérapie PCC avaient reçu plus fréquemment une première ligne de traitement antiviral antérieurement au PCC (77,8 % vs 20,6%; p <0,001). Il n'y avait pas de différence entre les deux groupes concernant l'échec à J28 (n=12; 33,3% vs n=10; 35,7%; p = 1). Les patients traités par bithérapie étaient plus fréquemment sevrés d'oxygène à J7 (n= 24; 72,7% vs n=12; 46.2%; p = 0.06), mais de façon non significative. Conclusion L'utilisation d'une bithérapie associant PCC et un antiviral d'action directe chez les patients immunodéprimés oxygénorequérant n'améliore pas le risque d'échec à J28. En revanche, la bithérapie pourrait permettre un sevrage en oxygène plus rapide. Des études portant sur de plus larges cohortes sont nécessaires pour préciser le rôle de cette bithérapie.

Data regarding tuberculosis (TB) in allogeneic hematopoietic stem cell transplant (Allo-HSCT) recipients in low areas of incidence is scarce. The objectives were to describe incidence, risk factors, clinical manifestations, treatment and outcome of tuberculosis after Allo-HSCT. We conducted a nationwide multicenter retrospective cohort study of adult Allo-HSCT recipients diagnosed with TB between 2012 and 2023 in France. Patients were identified through the SociétéFrancophone de Greffe de Moelle et de Thérapie cellulaire database. Each case was matched with 3 controls. Thirty-five patients were identified. The incidence rate was 60 per 100,000 patient-years. In multivariate analysis, being born in a high-incidence country for TB (OR = 19.4 [4.49-135.79], p < 0.001) was independently associated with TB. The median time from Allo-HSCT to TB diagnosis was 147 [range 30-7244] days. Extrapulmonary involvement was observed in 82% of cases (28/34). Median duration of anti-tuberculous therapy was 273 [range 10-424] days. Eight patients (25%) presented severe adverse reactions to anti-TB drugs. At the end of follow-up, two TB relapsed (6%). TB attributable mortality was 9% (N = 3, among a total of 7 deaths). Overall, our findings showed that TB post Allo-HSCT was rare and severe in low-incidence countries for TB, such as France. LTBI screening should be implemented for transplant candidates born in high-incidence countries for TB.

Introduction Paradoxical reaction (PR) aggravates the prognosis of central nervous system tuberculosis (CNS-TB). Yet, further characterisation is needed to optimise patients' management. Matériels et méthodes We retrospectively analysed 301 adults with CNS-TB between 2010 and 2023 across 10 hospitals. PR, defined as clinical or radiological deterioration after initial improvement, was assessed for predictors within 120 days using time-to-event analyses. A risk score was developed. Impact of PR on unfavourable outcomes (death or disability) was evaluated using multivariate logistic regression. Résultats Among 301 patients with CNS-TB, including 21·9% (n=66) HIV-positive, 37·9% (n=114) developed PR at a median of 48 days (IQR, 27–82) after treatment initiation, among which 87% (n=99/114) occurred within 120 days. Predictors for PR in univariate analysis included higher British Medical Research Council (BMRC) stage assessing neurological status (versus stage 1, p=0·085 for stage 2, p=0·003 for stage 3), low peripheral blood lymphocyte and CD4+ T cell counts (p=0·045 and p=0·015, respectively), CSF pleocytosis (p=0·010), M. tuberculosis identification in CSF (p=0·016), meningeal enhancement (p<0·001), cerebral vasculitis and infarction (p=0·001), and hydrocephalus (p=0·030). PR was associated with increased risk of unfavourable outcomes (adjusted OR 2·2, 95% CI 1·3–3·9). The risk score developed achieved an AUC of 0·68 for predicting PR within 120 days. Conclusion PR affects over one-third of CNS-TB patients, typically within the first two months, and are associated with worse outcomes. Clinical, inflammatory, and microbiological features may help predict PR, potentially guiding early monitoring and interventions.

Background Tuberculosis is a severe disease, not only due to its lethality but also to a significant morbidity occurring in people living with HIV (PLWH). If factors associated to mortality, severe morbidity and unsuccessful treatment related to the host are well identified in PLWH, there is scarce knowledge on factors related to the disease itself such as bacillary load, extent of lung involvement and disease dissemination to other organs. We sought to assess whether tuberculosis-related factors were associated with key patient outcomes in PLWH using data from an international clinical trial. Methods We conducted a secondary analysis of the ANRS 12300 Reflate TB2 international phase III open-label randomized trial that assessed different antiretroviral regimens in PLWH treated for tuberculosis. We evaluated whether bacillary load (smear positivity grade), extent of lung involvement (cavitation on chest x-ray) and disease dissemination (urine LAM positivity) were associated with mortality using Cox proportional hazard models and to severe morbidity and unsuccessful tuberculosis treatment using logistic regressions. Results Of 457 participants included in this study, 90 (20.4%) had grade 2 + or 3 + smear positivity, 39 (10.8%) had cavitation on chest X-ray, and 147 (32.2%) had a positive urinary LAM. Overall, 19 (4.2%) participants died, 113 (24.7%) presented severe morbidity, and 33 (7.2%) had unsuccessful tuberculosis treatment. Factors that remained independently associated with mortality were cavitation on chest x-ray (aHR = 7.92, 95% CI, 1.74–35.94, p = .0073) and LAM positivity (aHR = 5.53, 95% CI, 1.09–28.06, p = .0389). The only factor that remained significantly associated with severe morbidity was LAM positivity (aOR = 2.04, 95% CI, 1.06–3.92, p = .0323). No factor remained significantly associated with unsuccessful tuberculosis treatment. Conclusions In PLWH with tuberculosis enrolled in a trial, tuberculosis disease characteristics related to disease severity were cavitation on chest x-ray and urine LAM positivity. Early identification of these factors could help improve the management of PLWH with tuberculosis and improve their survival.

Introduction La tuberculose est la maladie infectieuse causant le plus de décès dans le monde. Le traitement standard d’une tuberculose pulmonaire repose sur un traitement par antibiothérapie pendant 6 mois. Le statut positif de la culture d’un prélèvement respiratoire à la recherche de Mycobacterium tuberculosis à 2 mois de traitement (M2) est le facteur prédictif d’échec de traitement ou de rechute le plus reconnu. Le but de notre étude est d’analyser les facteurs associés à une culture BK restant positive à M2 dans une population de tuberculoses traitées en France. Méthodes Nous avons analysé les données des patients inclus dans l’étude randomisée multicentrique française FAST-TB qui avaient une culture contributive à M2. Les patients ont été classés en culture positive ou négative à M2. Résultats Deux cent trois patients ont été inclus dans l’étude FAST-TB, parmi lesquels 177 sont venus à la consultation à M2 et 104 ont eu une culture contributive à M2, dont 82 une culture négative et 22 une culture positive. Nous avons retrouvé une association significative entre la persistance de la toux et des expectorations durant le suivi sous traitement et la positivité des cultures à M2. Il y a significativement plus de toux à M4 dans le groupe culture positive (71 % vs 36 %, p=0,006) (Fig. 1), significativement plus d’expectorations à M1 (84 % vs 50 %, p=0,009), à M2 (65 % vs 37 %, p=0,042) et à M4 (43 % vs 17 %, p=0,018). Enfin, on observe numériquement plus de cavernes (82 % vs 66 %, p=0,15) et d’atteintes parenchymateuses bilatérales (59 % vs 45 %, p=0,24) dans le groupe culture positive à M2. Conclusion Il semble important de contrôler la négativité des cultures des prélèvements respiratoires à M2 chez les patients en cours de traitement pour leur tuberculose, surtout en cas de symptômes respiratoires prolongés. La persistance des symptômes respiratoires durant le traitement pourrait faire partie des critères faisant discuter une éventuelle prolongation de la bithérapie de 3 mois supplémentaire.

Introduction Deux études ont évalué l'utilisation de traitements courts de 2 ou 4 mois pour la tuberculose (TB) pulmonaire. Les combinaisons associant isoniazide, rifapentine, moxifloxacine, pyrazinamide (HPMZ) pendant 4 mois ou bedaquilline, linézolide, isoniazide, pyrazinamide, ethambutol (BLHZE) pendant 2 mois étaient non-inférieures, en comparaison à la quadrithérapie standard. Or, certaines de ces molécules ne sont pas disponibles en France, ce qui limite la possibilité de proposer ces schémas de traitement aux patients éligibles. L'objectif de l'étude était d'étudier l'éligibilité aux traitements courts des cas de tuberculose diagnostiqués et suivis au sein du département de maladies infectieuses de notre hôpital. Matériels et méthodes Il s'agit d'une étude de cohorte rétrospective mono-centrique incluant les patients ayant initié un traitement antituberculeux dans le département de maladies infectieuses entre le 30/08/2021 et le 30/08/2023, en identifiant les cas à partir des déclarations obligatoires et des codes A15 à A19 du PMSI. Le critère de jugement principal était la proportion de participants inéligibles à un traitement court de type HPMZ ou BLHZE en appliquant les principaux critères d'inclusion/exclusion des deux essais cliniques. Les critères d'inéligibilité communs aux deux études étaient: grossesse ou allaitement, utilisation de fluoroquinolones (FQ) dans les 30 derniers jours, TB extra-pulmonaire (définie comme une localisation neurologique, osseuse ou péricardique pour HPMZ, et comme toute localisation hors ganglionnaire et pleurale pour BLHZE), présence d'un QT allongé, présence d'une résistance à la Rifampicine ou à l'Isoniazide. Les critères d'inégibilité spécifiques pour HPMZ étaient la présence d'une infection par le VIH avec moins de 100 CD4/mm3 ou une interaction médicamenteuse avec la rifampicine. Les critères d'inéligibilité pour BLHZE étaient l'âge≥65 ans, un antécédent de TB traitée, un diabète non contrôlé, une infection par le VIH, ou un cancer actif. Nous avons réalisé une analyse descriptive des proportions pour les différentes variables recueillies. Résultats Au total, 142 cas de tuberculoses ont été inclus dans cette analyse. L'âge médian [IQR] était 33 [26-45] ans, 23% étaient des femmes, 50% étaient nés en Afrique sub-saharienne, 20% étaient sans domicile fixe, 17% étaient bénéficiaires de l'aide médicale d'état et 15% sans couverture sociale. 51 (36%) étaient inéligibles au traitement HPMZ, principalement pour raison d'atteinte extra pulmonaire (n=15), d'interactions médicamenteuses avec les rifamycines (n=19), ou d'infection VIH avec <100 CD4/mm3 (n=5). 104 (73%) étaient inéligibles au traitement BLHZE, notamment du fait d'une localisation extra pulmonaire (n=81), d'un âge ≥65 ans (n=11), d'un antécédent de traitement d'une tuberculose (n=12) ou de comorbidités (diabète non contrôlé, n=11 ; infection VIH, n=11 ; cancer actif, n=6). Il n'y avait aucune résistance initiale à l'isoniazide ou à la rifampicine. Conclusion Dans notre étude rétrospective, la majorité des patients traités pour une tuberculose n'étaient pas éligibles à un traitement court de 2 ou 4 mois, essentiellement en raison d'un diagnostic de tuberculose extra-pulmonaire ou de comorbidités contre indiquant les traitements proposés dans ces régimes.

In a cohort of 72 consecutive virologically-suppressed patients with HIV-1 switching to long-acting cabotegravir and rilpivirine, we observed low cabotegravir trough concentrations 1 and 3 months after the first injection, with a significant association with no oral lead-in at 1 month [odds ratio (OR) = 6.3 [95% confidence interval (CI) 1.7–29.5], P = 0.01] and three months (OR = 5.6 [95% CI 1.3–29.7], P = 0.03), and with high BMI at 1 month (OR = 1.3 [95% CI 1.1–1.6], P = 0.007).

Background:The aim of this study was to assess the epidemiology, clinical manifestations, and outcome of mucormycosis over 15 years in a single center in France. Methods:We conducted a retrospective analysis of all mucormycosis cases in our institution from 1 January 2006 to 31 December 2020 and analyzed patients' medical records, laboratory results, and treatment to describe the epidemiology, clinical manifestations, diagnosis, treatment, and outcome. Mucorales quantitative polymerase chain reaction (qPCR) for the diagnosis was implemented in 2015. Results:Seventy-seven mucormycosis cases were analyzed in 77 patients, with a median age of 54 years (60% male). Identified risk factors were hematological diseases (46 cases [60%]), solid malignancies (2 cases), solid organ transplants (3), burns (18), diabetes only (7), and trauma (1). Sites of infection were lungs (42%), sinus (36%), skin (31%), central nervous system (9%), liver (8%), others (6%), and disseminated (12%). Diagnosis remained difficult and qPCR contributed to mucormycosis diagnosis in 30% of cases. Among hematology patients, serum qPCR was the only positive test in 15% of cases. A mixed mold infection was diagnosed in 24 of 77 (31%) patients. Surgical treatment was undertaken in 43 (56%) cases. Most patients received liposomal amphotericin B (89%), with a combination therapy in 18 of 77 cases (23%). Three-month survival rate was 40% (95% confidence interval [CI], .30-.53]). As for treatment, adjunction of surgery (hazard ratio, 0.47 [95%CI, .25-.91); P = 0.02) was associated with lower mortality. Conclusions:Mucormycosis remained associated with high mortality, especially in the hematological and burn populations. Surgery in combination with antifungal treatment was associated with improved survival.

Background Tixagevimab and cilgavimab (AZD7442) are two monoclonal antibodies developed by AstraZeneca for the pre-exposure prophylaxis and treatment of patients infected by SARS-CoV-2. Its effectiveness and safety in patients hospitalized with COVID-19 was not known at the outset of this trial.Methods DisCoVeRy is a phase 3, adaptive, multicentre, randomized, controlled trial conducted in 63 sites in Europe. Participants were randomly assigned (1:1) to receive placebo or tixagevimab-cilgavimab in addition to standard of care. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale. Several clinical, virological, immunological and safety endpoints were also assessed.Findings Due to slow enrolment, recruitment was stopped on July 1st, 2022. The antigen positive modified intention-to-treat population (mITT) was composed of 173 participants randomized to tixagevimab-cilgavimab (N = 91) or placebo (N = 82), 91.9% (159/173) with supplementary oxygen, and 47.4% (82/173) previously vaccinated at inclusion. There was no significant difference in the distribution of the WHO ordinal scale at day 15 between the two groups (odds ratio (OR) 0.93, 95%CI [0.54-1.61]; p = 0.81) nor in any clinical, virological or safety secondary endpoints. In the global mITT (N = 226), neutralization antibody titers were significantly higher in the tixagevimab-cilgavimab group/patients compared to placebo at day 3 (Least-squares mean differences (LSMD) 1.44, 95% Confidence interval (CI) [1.20-1.68]; p < 10−23) and day 8 (LSMD 0.91, 95%CI [0.64-1.18]; p < 10−8) and it was most important for patients infected with a pre-omicron variant, both at day 3 (LSMD 1.94, 95% CI [1.67-2.20], p < 10−25) and day 8 (LSMD 1.17, 95% CI [0.87-1.47], p < 10−9), with a significant interaction (p < 10−7 and p = 0.01 at days 3 and 8, respectively).Interpretation There were no significant differences between tixagevimab-cilgavimab and placebo in clinical endpoints, however the trial lacked power compared to prespecified calculations. Tixagevimab-cilgavimab was well tolerated, with low rates of treatment related events.Funding Trial registration: [ClinicalTrials.gov][1] [NCT04315948][2]. Registered on 13 March 2020 updated on 22 April 2021.### Competing Interest StatementM.H. reports grants from The Belgian Center for Knowledge (KCE), the Fonds Erasme-COVID-Université Libre de Bruxelles and the EU-Horizon program, for the submitted work; and has received support for attending meetings from Pfizer; support for participation on an advisory board for therapeutics on COVID-19; and support for leadership for the Belgian guidelines on therapeutics for COVID-19 and acting as a treasurer for the Belgian Society of Clinical Microbiology and Infectious Diseases. R.G. reports consulting fees from Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, Abbvie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankvo; lecture fees from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, Abbvie, Gilead, and Daiichi Sankvo; support for attending meetings from Roche, Amgen, Janssen, AstraZeneca, Novartis, Merck Sharp & Dohme, Celgene, Gilead, Bristol Myers Squibb, Abbvie, and Daiichi Sankvo; participation in a Data Safety and Monitoring Board for Celgene, Novartis, Roche, Bristol Myers Squibb, Takeda, Abbvie, AstraZeneca, Janssen, Merck Sharp & Dohme, Merck, Gilead, and Daiichi Sankyo; research grants from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, Bristol Myers Squibb, Merck Sharp & Dohme, Sandoz, Abbvie, Gilead, and Daiichi Sankyo. J.-A.P. reports consulting fees from Pfizer, Merck Sharp & Dohme, and Janssen-Cilag; lecture fees from Pfizer; and support for attending meetings from Pfizer. D.C. reports grants and lecture fees from Janssen and lecture fees from Gilead, outside the submitted work. C.B. reports participation in a Data Safety and Monitoring Board for 4Living Biotech; and consulting fees from Da Volterra and Mylan Pharmaceuticals, outside the submitted work. F.M. reports grants and consulting fees from Da Volterra, grants from Sanofi, and consulting fees from Ipsen, outside the submitted work. All other authors declare no competing interests.### Clinical TrialNCT04315948### Funding StatementThis work received funding from several sources: the European Commission (EU-Response, Grant 101015736), the DIM One Health Ile-de-France (R20117HD) and Astra-Zeneca. We thank all participants who consented to enroll in the trial, as well as all study and site staff whose indispensable assistance made the conduct of the DisCoVeRy trial possible (all listed in the appendix, pp 27-36)### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethics committee of the BASG (Bundesamt fur Sicherheit im Gesundheitswesen), Austria, gave ethical approval for this work. Ethics committee of the FAMHP (Federal Agency for Medicines and Health Products), Belgium, gave ethical approval for this work. Ethics committee of the SUKL (Statni Ustav Pro Kontrolu Leciv), Czech Republic, gave ethical approval for this work. Ethics committee of the ANSM (Agence nationale de securite du medicament et des produits de sante), France, gave ethical approval for this work. Ethics committee of the National Organization for Medicines, Greece, gave ethical approval for this work. Ethics committee of the National Institute of Pharmacy and Nutrition (OGYEI), Hungary, gave ethical approval for this work. Ethics committee of the HPRA (Health Products Regulatory Authority), Ireland, gave ethical approval for this work. Ethics committee of the CNER (Comite National d Ethique de Recherche, ministere de la sante), Luxembourg, gave ethical approval for this work. Ethics committee of the NOMA (Norwegian Medical Products Agency), Norway, gave ethical approval for this work. Ethics committee of the Komisja Bioetyczna Przy Uniwersytecie Medycznym W Lodzi, Poland, gave ethical approval for this work. Ethics committee of the Infarmed (National Authority of Medicines and Health Products), Portugal, gave ethical approval for this work. Ethics committee of the SULK (Statni ustav pro kontrolu leciv), Slovakia, gave ethical approval for this work. Ethics committee of the AEMPS (Agencia Espanola de Medicamentos y Productos Sanitarios), Spain, gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesWith publication, deidentified, individual participant data that underlie this Article, along with a data dictionary describing variables in the dataset, will be made available to researchers whose proposed purpose of use is approved by the DisCoVeRy Steering Committee. To request the dataset, please address directly to the corresponding author (florence.ader@chu-lyon.fr) or to the sponsor's representative (helene.esperou{at}inserm.fr) to obtain a data access form. All requests will be evaluated by the Trial Management Team and the DisCoVeRy Steering Committee. For accepted requests, data will be shared after signing a data transfer agreement with the study sponsor. Data will be shared directly or through access on the INSERM repository. Related documents, such as the study protocol, statistical analysis plan, and informed consent form, will be made available (with publication) on request to the corresponding author or to the sponsor's representative. The data will be open access for the informed consent form, protocol, and statistical analysis plan. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04315948&atom=%2Fmedrxiv%2Fearly%2F2024%2F02%2F24%2F2024.02.23.24302586.atom

Introduction Tuberculosis (TB) is a leading infectious cause of death globally. It is the most common opportunistic infection in people living with HIV, and the most common cause of their morbidity and mortality. Following TB treatment, surviving individuals may be at risk for post-TB lung disease. The TB Sentinel Research Network (TB-SRN) provides a platform for coordinated observational TB research within the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium.Methods and analysis This prospective, observational cohort study will assess treatment and post-treatment outcomes of pulmonary TB (microbiologically confirmed or clinically diagnosed) among 2600 people aged ≥15 years, with and without HIV coinfection, consecutively enrolled at 16 sites in 11 countries, across 6 of IeDEA’s global regions. Data regarding clinical and sociodemographic factors, mental health, health-related quality of life, pulmonary function, and laboratory and radiographic findings will be collected using standardised questionnaires and data collection tools, beginning from the initiation of TB treatment and through 12 months after the end of treatment. Data will be aggregated for proposed analyses.Ethics and dissemination Ethics approval was obtained at all implementing study sites, including the Vanderbilt University Medical Center Human Research Protections Programme. Participants will provide informed consent; for minors, this includes both adolescent assent and the consent of their parent or primary caregiver. Protections for vulnerable groups are included, in alignment with local standards and considerations at sites. Procedures for requesting use and analysis of TB-SRN data are publicly available. Findings from TB-SRN analyses will be shared with national TB programmes to inform TB programming and policy, and disseminated at regional and global conferences and other venues.

Introduction Les pneumopathies dues à Haemophilus influenzae sont des pathologies fréquentes mais mal décrites. L’objectif de cette étude est de décrire la sévérité des pneumopathies à H. influenzae et la fréquence des récurrences après le traitement d’un premier épisode. Patients et méthodes Nous avons conduit une étude rétrospective multicentrique incluant des patients de 6 hôpitaux universitaires parisiens, ayant consulté entre le 1er septembre 2022 et le 31 août 2023.Les patients éligibles étaient identifiés via les registres des laboratoires de bactériologie et via le système de codage informatique (PMSI).Une pneumopathie à Haemophilus influenzae (Hi) était définie par la combinaison de 5 items : la présence de symptômes respiratoires aigus, un syndrome inflammatoire, une nouvelle image pulmonaire compatible avec une bronchopneumopathie, un prélèvement respiratoire positif à Hi et un traitement antibiotique à visée respiratoire débuté par le clinicien.Une récurrence certaine était définie par la réapparition des symptômes dans les 3 mois, avec un nouveau prélèvement respiratoire positif à Hi. Une récurrence probable était définie par la réapparition des symptômes dans le mois, sans aucune documentation microbiologique. La sévérité était définie par la nécessité d’une oxygénothérapie avec un débit>3L/min, un passage en réanimation ou un décès imputable à l’infection pulmonaire. Résultats Au total, 135 patients (âge moyen : 59,4 ans, 60,7 % d’hommes) avec un premier épisode de pneumopathie à H. influenzae ont été inclus. Parmi eux, 34,8 % avaient une pneumopathie sévère (14,1 % étaient hospitalisés en réanimation). De plus, 49,6 % étaient immunodéprimés, (17,0 % avaient une immunodépression cellulaire, 17,8 % une immunodépression humorale et 14,8 % avaient immunodépression combinée).La durée moyenne d’antibiothérapie reçue par les patients pour un épisode était de 8,1 jours.Quarante et un patients (30,4 %) ont présenté au moins une récurrence de pneumopathie à H. influenzae (23 certaines, 18 probables).Les facteurs associés à une récurrence étaient le contact prolongé avec de jeunes enfants (p=0,003), un déficit immunitaire primitif (100 % de déficit combiné ou humoral) (p=0,006), une hémopathie maligne (87,5 % d’hémopathie maligne B et de myélome) (p=0,021), un dosage pondéral en IgA faible (<0,7g/L) (p<0,001), un dosage pondéral en IgM faible (<0,4g/L) (p=0,002).Les patients avec des pneumopathies récurrentes étaient significativement plus jeunes (p=0,005) et avaient un indice de masse corporel significativement plus faible (p=0,010) que les patients n’ayant présenté de récurrence. Une pathologie pulmonaire chronique, la BPCO, le tabac, la co-infection virale n’étaient pas significativement liés à un risque de récurrence. Conclusion Nos résultats préliminaires suggèrent un risque important de récurrence pour les pneumopathies à Hi (30,4 %). Notre travail suggère un rôle important de l’immunité humorale.

Background The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. Methods In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. Findings Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference –0·5, –11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. Interpretation Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. Funding ViiV Healthcare.

Background After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART.Methods We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS.Results Of 460 trial participants, 453 from Brazil, Cote d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm(3), and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 <= 100 cells/mu L, HIV RNA >= 500 000 copies/mL, and extrapulmonary/disseminated TB.Conclusions We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS. Integrase strand transfer inhibitor-based antiretroviral therapy (ART) did not increase the risk of tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in the Reflate TB2 randomized controlled trial. Low CD4 counts and high HIV-RNA at ART initiation and extrapulmonary/disseminated TB were risk factors for TB-IRIS.

We report the case of an allogeneic stem cell transplant recipient with nosocomial acquisition of SARS-CoV-2 infection who received antispike neutralizing monoclonal antibody bamlanivimab 2 days after diagnosis of SARS-CoV-2 infection but progressed to severe COVID-19 pneumonia and died with the selection of E484K/Q resistance mutations to bamlanivimab.

Qualitative SARS-CoV-2 antigen assays based on immunochromatography are useful for mass diagnosis of COVID-19, even though their sensitivity is poor in comparison with RT-PCR assays. In addition, quantitative assays could improve antigenic test performance and allow testing with different specimens. Using quantitative assays, we tested 26 patients for viral RNA and N-antigen in respiratory samples, plasma and urine. This allowed us to compare the kinetics between the three compartments and to compare RNA and antigen concentrations in each. Our results showed the presence of N-antigen in respiratory (15/15, 100%), plasma (26/59, 44%) and urine (14/54, 28.9%) samples, whereas RNA was only detected in respiratory (15/15, 100%) and plasma (12/60, 20%) samples. We detected N-antigen in urine and plasma samples until the day 9 and day 13 post-inclusion, respectively. The antigen concentration was found to correlate with RNA levels in respiratory (p < 0.001) and plasma samples (p < 0.001). Finally, urinary antigen levels correlated with plasma levels (p < 0.001). Urine N-antigen detection could be part of the strategy for the late diagnosis and prognostic evaluation of COVID-19, given the ease and painlessness of sampling and the duration of antigen excretion in this biological compartment.

ObjectiveTo evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial).DesignOpen label, randomised clinical trial.SettingCORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021.Participants120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression.InterventionsOpen label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40.Main outcome measuresPrimary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids.Results120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10).ConclusionsIn this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further.Trial registrationClinicalTrials.govNCT04345991.