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We describe pulmonary cryptococcosis in a 28-year-old previously healthy man. Exhaustive immunological investigations revealed a primary NK cell deficiency associated with a secondary impaired anti- Cryptococcus CD8 lymphocyte response and the expansion of a CD8Vβ14 + T cell clone. This case illustrates the potential role of NK cells in immunity against Cryptococcus .

Background Tick-borne lymphadenopathy (TIBOLA) is a tick-borne disease transmitted by Dermacentor ticks and is usually caused by Rickettsia . In 2021, clinicians in northeastern France reported an increase in TIBOLA cases. Methods This entomo-clinical, multicenter, retrospective, and observational study aimed to describe the evolution of the number of TIBOLA cases between 2016 and 2021 in northeastern France as well as the evolution of the Dermacentor tick population. Results A total of 35 cases of TIBOLA were identified, 16 of which occurred in 2021, with clear predominance in April and May. A longitudinal study performed in the Alsace region (endemic for ticks and tick-borne diseases) revealed a peak in tick activity in 2021. A trend toward an increase in TIBOLA cases in 2021 in the northeastern region of France was observed, as was an increase in the Dermacentor tick population in some biotopes. Conclusions TIBOLA appears to be an emerging disease that should be monitored, as should the Dermacentor population. Graphical Abstract

Heterozygous missense mutations leading to a gain of function (GOF) are the most frequent genetic cause of chronic mucocutaneous candidiasis (CMC). We describe the case of a patient presenting a new GOF mutation of with the clinical symptoms of CMC, recurrent pneumonia, and persistent central erythema with papulopustules with ocular involvement related to rosacea-like demodicosis. Genetic analysis targeted next-generation sequencing (NGS; NGS panel DIPAI v.1) exploring the 98 genes most frequently involved in primary immunodeficiencies, including , was performed to identify an underlying genetic defect. NGS identified a novel variant of , c.884C>A (exon 10), p.T295Y, not previously described. This variant was found to be gain of function using an luciferase reporter assay. Rosacea-like demodicosis was confirmed by substantial proliferation observed the microscopic examination of a cutaneous sample. A review of literature retrieved 20 other cases of GOF mutations associated with early-onset rosacea-like demodicosis, most with ocular involvement. We describe a new GOF mutation associated with a phenotype of CMC and rosacea-like demodicosis. Rosacea-like demodicosis appears as a novel and important clinical phenotype among patients with GOF mutation.

To the Editor: In their review article, Vannier and Krause (June 21 issue) 1 describe the classic form of Babesia divergens infections. B. divergens is responsible for most infections in Europe (approximately 40 reported cases); these are mainly severe infections in persons who have undergone splenectomy. In 2009, we diagnosed two cases of babesiosis in northeastern France in two young, healthy people, 15 days after they received tick bites. They had a marked flulike syndrome and a low level of parasitemia. 2 Both patients had a suggestive positive blood smear, though only one was clearly identified as being infected with B. divergens . . .

The antiviral efficacy of remdesivir against SARS-CoV-2 is still controversial. We aimed to evaluate the clinical efficacy of remdesivir plus standard of care compared with standard of care alone in patients admitted to hospital with COVID-19, with indication of oxygen or ventilator support. DisCoVeRy was a phase 3, open-label, adaptive, multicentre, randomised, controlled trial conducted in 48 sites in Europe (France, Belgium, Austria, Portugal, Luxembourg). Adult patients (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and illness of any duration were eligible if they had clinical evidence of hypoxaemic pneumonia, or required oxygen supplementation. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, any contraindication to one of the studied treatments or their use in the 29 days before random assignment, or use of ribavirin, as well as pregnancy or breastfeeding. Participants were randomly assigned (1:1:1:1:1) to receive standard of care alone or in combination with remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, or hydroxychloroquine. Randomisation used computer-generated blocks of various sizes; it was stratified on severity of disease at inclusion and on European administrative region. Remdesivir was administered as 200 mg intravenous infusion on day 1, followed by once daily, 1-h infusions of 100 mg up to 9 days, for a total duration of 10 days. It could be stopped after 5 days if the participant was discharged. The primary outcome was the clinical status at day 15 measured by the WHO seven-point ordinal scale, assessed in the intention-to-treat population. Safety was assessed in the modified intention-to-treat population and was one of the secondary outcomes. This trial is registered with the European Clinical Trials Database, EudraCT2020-000936-23, and ClinicalTrials.gov, NCT04315948. Between March 22, 2020, and Jan 21, 2021, 857 participants were enrolled and randomly assigned to remdesivir plus standard of care (n=429) or standard of care only (n=428). 15 participants were excluded from analysis in the remdesivir group, and ten in the control group. At day 15, the distribution of the WHO ordinal scale was: (1) not hospitalised, no limitations on activities (61 [15%] of 414 in the remdesivir group vs 73 [17%] of 418 in the control group); (2) not hospitalised, limitation on activities (129 [31%] vs 132 [32%]); (3) hospitalised, not requiring supplemental oxygen (50 [12%] vs 29 [7%]); (4) hospitalised, requiring supplemental oxygen (76 [18%] vs 67 [16%]); (5) hospitalised, on non-invasive ventilation or high flow oxygen devices (15 [4%] vs 14 [3%]); (6) hospitalised, on invasive mechanical ventilation or extracorporeal membrane oxygenation (62 [15%] vs 79 [19%]); (7) death (21 [5%] vs 24 [6%]). The difference between treatment groups was not significant (odds ratio 0·98 [95% CI 0·77–1·25]; p=0·85). There was no significant difference in the occurrence of serious adverse events between treatment groups (remdesivir, 135 [33%] of 406 vs control, 130 [31%] of 418; p=0·48). Three deaths (acute respiratory distress syndrome, bacterial infection, and hepatorenal syndrome) were considered related to remdesivir by the investigators, but only one by the sponsor's safety team (hepatorenal syndrome). No clinical benefit was observed from the use of remdesivir in patients who were admitted to hospital for COVID-19, were symptomatic for more than 7 days, and required oxygen support. European Union Commission, French Ministry of Health, Domaine d'intérêt majeur One Health Île-de-France, REACTing, Fonds Erasme-COVID-Université Libre de Bruxelles, Belgian Health Care Knowledge Centre, Austrian Group Medical Tumor, European Regional Development Fund, Portugal Ministry of Health, Portugal Agency for Clinical Research and Biomedical Innovation. For the French translation of the abstract see Supplementary Materials section.

Human granulocytic anaplasmosis (HGA), caused by Anaplasma phagocytophilum transmitted through tick bites, remains poorly documented in France. We conducted a retrospective, multicenter study of cases in Alsace during 2012-2024, including 39 HGA episodes in 38 patients PCR positive for A. phagocytophilum. Most (63.2%) patients were men, median age was 60.5 years, and 76.3% lived in rural areas. A tick bite was reported in 61.6% of cases. Frequent symptoms included fever (97.4%), fatigue (61.5%), and headache (61.5%). Laboratory findings showed elevated C-reactive protein (100%), thrombocytopenia (94.9%), leukopenia (59.0%), and cytolysis (66.7%). One patient had secondary hemophagocytic lymphohistiocytosis. Most (87.2%) patients were hospitalized; none required intensive care unit admission. Doxycycline was administered in 29 cases, and all patients recovered. HGA should be considered in febrile patients with recent tick exposure and cytopenia. Although often benign, rare severe HGA forms can occur and justify increased clinical awareness, especially in A. phagocytophilum-endemic areas.

Herpes simplex virus type 2 (HSV-2) is a common cause of infection, which is usually self-limited and asymptomatic. A 71-year-old patient with HSV-2 primo-infection developed acute hepatitis and secondary hemophagocytic lymphohistiocytosis. The patient had high levels of autoantibodies against type I interferon (IFN) (> 1000 ng/mL), neutralizing high concentration (10 ng/mL) of both IFN-α and IFN-ω but not IFN-β. Anti-IFN-I auto-antibodies are rarely observed in healthy individuals; however, their prevalence increases in individuals over 70 years of age and have been identified as a cause of some severe viral diseases, including critical COVID-19. Considering the function of IFN-I in innate immunity, the pathological role of these autoantibodies in severe viral diseases following primo-infections in elderly patient appears crucial.

An epidemic of Mycoplasma pneumoniae infection has been observed in France since September, 2023. We aimed to describe the characteristics of adults hospitalised for M pneumoniae infection and identify factors associated with severe outcomes of infection. MYCADO is a retrospective observational study including adults hospitalised for 24 h or more in 76 hospitals in France for a M pneumoniae infection between Sept 1, 2023, and Feb 29, 2024. Clinical, laboratory, and imaging data were collected from medical records. We identified factors associated with severe outcomes of infection, defined as a composite of intensive care unit (ICU) admission or in-hospital death, using multivariable logistic regression. 1309 patients with M pneumoniae infection were included: 718 (54·9%) were men and 591 (45·1%) were women; median age was 43 years (IQR 31–63); 288 (22·0%) had chronic respiratory failure; 423 (32·3%) had cardiovascular comorbidities; and 105 (8·0%) had immunosuppression. The most common symptoms were cough (1098 [83·9%]), fever (1023 [78·2%]), dyspnoea (948 [72·4%]), fatigue (550 [42·0%]), expectorations (473 [36·1%]), headache (211 [16·1%]), arthromyalgia (253 [19·3%]), ear, nose, and throat symptoms (202 [15·4%]), diarrhoea (138 [10·5%]), and vomiting (132 [10·1%]). 156 (11·9%) of 1309 patients had extra-respiratory manifestations, including 36 (2·8%) with erythema multiforme, 19 (1·5%) with meningoencephalitis, 44 (3·4%) with autoimmune haemolytic anaemia, and 17 (1·3%) with myocarditis. The median hospital stay was 8 days (IQR 6–11). 424 (32·4%) patients had a severe outcome of infection, including 415 (31·7%) who were admitted to the ICU and 28 (2·1%) who died in hospital. Those more likely to present with severe outcomes of infection were patients with hypertension, obesity, chronic liver failure, extra-respiratory manifestations, pulmonary alveolar consolidation or bilateral involvement on CT scan, as well as elevated inflammatory markers, lymphopenia or neutrophilic polynucleosis, and those who did not versus did receive any antibiotic active against M pneumoniae before admission. This national, observational study highlighted unexpected, atypical radiological presentations, a high proportion of transfers to the ICU, and an association between severity and delayed administration of effective antibiotics. This should remind clinicians that no radiological presentation can rule out M pneumoniae infection, and encourage them to reassess patients early after prescribing a β-lactam, or even to discuss prescribing macrolides as first-line treatment in the context of an epidemic. None. For the French translation of the abstract see Supplementary Materials section.

We aimed to describe the clinical characteristics, management, and residual symptoms (RS) in patients with definite and possible Lyme neuroborreliosis (LNB). We conducted a retrospective French multicenter cohort study (2010–2020). Cases of LNB were defined as clinical manifestations attributed to LNB and a positive Borrelia -specific intrathecal antibody index (AI) (“possible” LNB) and with pleocytosis (“definite” LNB). Risk factors of RS were determined using a logistic regression model. We included 138 adult patients with a positive AI. Mean age was 59.5 years (± 14.7). The median duration of symptoms before diagnosis was 1.0 [0.5–4.0] months. The most frequent manifestation was radicular pain ( n  = 79, 57%). Complete cerebrospinal fluid (CSF) leukocyte analysis was available in 131 patients, of whom 72 (55%) had pleocytosis. Patients with definite LNB had a shorter duration of symptoms (median 1.0 [0.5–2.6] vs. 3.0 [0.6–7.0] months, p  < 0.01) and more radicular pain (74% vs 44%, p  < 0.01) than patients with possible LNB. At the last visit (median duration of follow-up: 70 [30–175] days), 74/124 patients (59.7%) reported RS, mostly radicular pain ( n  = 31, 25%). In multivariate analysis, definite LNB (OR = 0.21 [0.05–0.931], p  = 0.039) and duration of symptoms less than 3 months (OR = 0.04 [0.01–0.37], p  = 0.005) were protective factors against RS at last follow-up. Our study highlights the challenges of LNB management, especially for patients with a positive AI without pleocytosis, questioning whether LB is still ongoing or not. Early diagnosis and treatment are important to improve outcomes and to lower potential RS.

Eligible participants were adults (aged ≥18 years) who were admitted to hospital with a positive PCR test for SARS-CoV-2 (<72 h before randomisation) and also had pulmonary rales or crackles with a peripheral oxygen saturation of 94% or less or required supplemental oxygen. Similar to findings from preliminary analyses, participants from the remdesivir group who were not on mechanical ventilation or ECMO when they were randomly assigned to a treatment group (n=692) had a significantly longer time to the composite endpoint of new mechanical ventilation, ECMO, or death in the 29 days following randomisation than did the control group (cumulative incidence in the remdesivir group was 58 [17%] of 343 participants vs 88 [25%] of 349 in the control group; adjusted hazard ratio [HR] 0·63 [95% CI 0·45–0·88]; p=0·010). In non-prespecified analyses, this effect was significant in participants with severe disease when they were randomly assigned to a treatment group (cumulative incidence in the remdesivir group 25 [29%] of 87 vs 47 [50%] of 94 in the control group; unadjusted HR 0·49 [95% CI 0·30–0·80]; p=0·0040) but not in those with moderate disease (33 (13%) of 256 vs 41 (16%) of 255; 0·79 [0·50–1·25]; p=0·31).