Background We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. Methods In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov , NCT04501978 . Findings Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–...

During the past decade the proportion of non-infectious inflammatory diseases in FUO series has increased. Based on our findings we recommend: (1) a PET/CT scan be performed early in the diagnostic work-up of patients with FUO, and (2) restraint in performing invasive procedures in patients with FUO in whom no cause of fever has been determined during diagnostic work-up.

The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide registration, clinical information and laboratory findings were collected from all 65 confirmed cases of H. influenzae meningitis during the period 1994-2005. Twenty-nine patients (45%) were <13 years old [median 15 months (range 0-147)], and 36 patients (55%) were >24 years old [median 62 years (range 25-96)]. Hib accounted for 31% (20/65) of the cases, and significantly more children were infected with Hib compared with adults [53% (16/29) vs. 11% (4/36), respectively, p 0.0003]. Overall, 38% of cases had an otogenic focus and this was thus the most frequent primary focus of infection. Among children infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83-96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults. The presence of a lung focus was an independent prognostic factor for an unfavourable outcome (p 0.03). In conclusion, meningitis caused by Hib has been infrequent in Denmark after introduction of the Hib vaccine in the childhood vaccination programme, and no increase in meningitis cases due to non-b type H. influenzae has been observed. Cases with H. influenzae meningitis frequently had an otogenic focus, with low risk of an unfavourable outcome.

Background A substantial body of evidence has recently emphasized the risks associated with antibiotic resistance (ABR) in conflicts in the Middle East. War-related, and more specifically weapon-related wounds can be an important breeding ground for multidrug resistant (MDR) organisms. However, the majority of available evidence comes from the military literature focused on risks and patterns of ABR in infections from combat-related injuries among military personnel. The overall aim of this study is to contribute to the scarce existing evidence on the burden of ABR among patients, including civilians with war-related wounds in the Middle East, in order to help inform the revision of empirical antibiotic prophylaxis and treatment protocols adopted in these settings. The primary objectives of this study are to: 1) describe the microbiology and the corresponding resistance profiles of the clinically relevant bacteria most commonly isolated from skin, soft tissue and bone biopsies in patients admitted to the WTTC; and 2) describe the association of the identified bacteria and corresponding resistance profiles with sociodemographic and specimen characteristics. Methods We retrospectively evaluated the antibiograms of all consecutive, non-duplicate isolates from samples taken from patients admitted to the ICRC WTTC between 2016 and 2019, limited to skin and soft tissue samples and bone biopsies. We collected data on socio-demographic characteristics from patient files and data on specimens from the WHONET database. We ran univariate and multivariable logistic regression models to test the association between bacterial and resistance profiles with sociodemographic and specimen characteristics. Results Patients who were admitted with war-related trauma to the ICRC reconstructive surgical project in Tripoli, Lebanon, from 2016 to 2019, presented with high proportion of MDR in the samples taken from skin and soft tissues and bones, particularly Enterobacterales (44.6%), MRSA (44.6%) and P. aeruginosa (7.6%). The multivariable analysis shows that the odds of MDR isolates were higher in Iraqi patients (compared to Syrian patients) and in Enterobacterales isolates (compared to S. aureus isolates). Conclusions Our findings stress the importance of regularly screening patients who present with complex war-related injuries for colonization with MDR bacteria, and of ensuring an antibiotic-sensitivity testing-guided antimicrobial therapeutic approach.

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Infections with Burkholderia pseudomallei (melioidosis) are rare events in Scandinavian countries, but the bacterium may be contracted during travel to endemic areas, i.e. Southeast Asia (especially Thailand) and northern Australia. Here, 5 travel-related cases occurring within the last 3 y in Denmark are reported, with particular emphasis on diagnostic and therapeutic challenges posed to health staff with little experience in the management of melioidosis. A newly developed B. pseudomallei-specific polymerase chain reaction test was applied and was able to correctly identify all isolates.

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Background: Neurological complications during and after SARS-CoV-2 infection have been frequently described. The detection of either SARS-CoV-2 RNA or specific antibodies against SARS-CoV-2 in cerebrospinal fluid in the context of concomitant neurological manifestations indicates neuroinfection. Methods and Results: This is a retrospective descriptive analysis of cerebrospinal fluids and serum samples from 2 hospitalized patients and autopsy findings from 2 patients who died at home. Samples were analysed by 3 independent enzyme-linked immunosorbent assays. Specific antibodies against SARS-CoV-2 were detected in cerebrospinal fluids and paired serum in all 4 cases. Levels of antibodies in cerebrospinal fluids were highest in samples from a deceased man with critical progression of COVID-19 and detectable SARS-CoV-2 viral RNA in cerebrospinal fluid, serum, 4 brain biopsies and 15 additional tissue samples, though immunohistochemical staining for SARS-CoV-2 in brain tissue did not detect the virus. Conclusion: Detection of SARS-CoV-2 antibodies in paired serum and cerebrospinal fluid may support the presence of SARS-CoV-2 neuroinflammatory disease in patients with COVID-19 and neurological manifestations.