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BackgroundLopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a and hydroxychloroquine efficacy for COVID-19 have been evaluated, but detailed evaluation is lacking.ObjectiveTo determine the efficacy of lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a, hydroxychloroquine or remdesivir for improving the clinical, virological outcomes in COVID-19 inpatients.DesignOpen-label, randomized, adaptive, controlled trial.SettingMulti-center trial with patients from France.Participants583 COVID-19 inpatients requiring oxygen and/or ventilatory supportInterventionStandard of care (SoC, control), SoC plus lopinavir/ritonavir (400 mg lopinavir and 100 mg ritonavir every 12h for 14 days), SoC plus lopinavir/ritonavir plus IFN-ß-1a (44 μg of subcutaneous IFN-ß-1a on days 1, 3, and 6), SoC plus hydroxychloroquine (400 mg twice on day 1 then 400 mg once daily for 9 days) or SoC plus remdesivir (200 mg intravenously on day 1 then 100 mg once-daily for hospitalization duration or 10 days).MeasurementsThe primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens and safety analyses.ResultsAdjusted Odds Ratio (aOR) for the WHO 7-point ordinal scale were not in favor of investigational treatments: lopinavir/ritonavirversuscontrol, aOR 0.83, 95%CI, 0.55 to 1.26, P=0.39; lopinavir/ritonavir-IFN-β-1aversuscontrol, aOR 0.69, 95%CI, 0.45 to 1.04, P=0.08; hydroxychloroquineversuscontrol, aOR 0.93, 95%CI, 0.62 to 1.41, P=0.75. No significant effect on SARS-CoV-2 RNA clearance in respiratory tract was evidenced. Lopinavir/ritonavir-containing treatments were significantly associated with more SAE.LimitationsNot a placebo-controlled, no anti-inflammatory agents tested.ConclusionNo improvement of the clinical status at day 15 nor SARS-CoV-2 RNA clearance in respiratory tract specimens by studied drugs. This comforts the recent Solidarity findings.RegistrationNCT04315948.FundingPHRC 2020, Dim OneHealth, REACTing

International audience; PURPOSE: Infectious encephalitis (IE) is a severe disease which requires intensive care unit (ICU) admission in up to 50% of cases. We aimed to describe characteristics, management and outcomes of IE patients who required ICU admission. MATERIALS AND METHODS: Ancillary study focusing on patients with ICU admission within the ENCEIF cohort, a French prospective observational multicentre study. The primary criteria for outcome was the functional status at hospital discharge, categorized using the Glasgow outcome scale (GOS). Logistic regression model was used to identify risk factors for poor outcome, defined as a GOS ≤ 3. RESULTS: We enrolled 198 ICU patients with IE. HSV was the primary cause (n = 72, 36% of all IE, 53% of IE with microbiological documentation). Fifty-two patients (26%) had poor outcome at hospital discharge, including 22 deaths (11%). Immunodeficiency, supratentorial focal signs on admission, lower cerebrospinal fluid (CSF) white cells count (2 days were independent predictors of poor outcome. CONCLUSION: HSV is the primary cause of IE requiring ICU admission. IE patients admitted in ICU have a poor prognosis with 11% of in-hospital mortality and 15% of severe disabilities in survivors at discharge.

Objectives Initial studies of individuals with coronavirus disease 2019 (COVID-19) revealed that obesity, diabetes and hypertension were associated with severe outcomes. Subsequently, some authors showed that the risk could vary according to age, gender, co-morbidities and medical history. In a nationwide retrospective cohort, we studied the association between these co-morbidities and patients' requirement for invasive mechanical ventilation (IMV) or their death. Methods All French adult inpatients with COVID-19 admitted during the first epidemic wave (February to September 2020) were included. When patients were diagnosed with obesity, diabetes or hypertension for the first time in 2020, these conditions were considered as incident co-morbidities, otherwise they were considered prevalent. We compared outcomes of IMV and in-hospital death according to obesity, diabetes and hypertension, taking age, gender and Charlson's co-morbidity index score (CCIS) into account. Results A total of 134 209 adult inpatients with COVID-19 were included, half of them had hypertension (n = 66 613, 49.6%), one in four were diabetic (n = 32 209, 24.0%), and one in four were obese (n = 32 070, 23.9%). Among this cohort, IMV was required for 13 596 inpatients, and 19 969 patients died. IMV and death were more frequent in male patients (adjusted oods ratio (aOR) 2.0, 95% CI 1.9–2.1 and aOR 1.5, 95% CI 1.4–1.5, respectively), IMV in patients with co-morbidities (aOR 2.1, 95% CI 2.0–2.2 for CCIS = 2 and aOR 3.0, 95% CI 2.8–3.1 for CCIS ≥5), and death in patients aged 80 or above (aOR 17.0, 95% CI 15.5–18.6). Adjusted on age, gender and CCIS, death was more frequent among inpatients with obesity (aOR 1.2, 95% CI 1.1–1.2) and diabetes (aOR 1.2, 95% CI 1.1–1.2). IMV was more frequently necessary for inpatients with obesity (aOR 1.9, 95% CI 1.8–2.0), diabetes (aOR 1.4, 95% CI 1.3–1.4) and hypertension (aOR 1.7, 95% CI 1.6–1.8). Comparatively, IMV was more often required for patients with the following incident co-morbidities: obesity (aOR 3.5, 95% CI 3.3–3.7), diabetes (aOR 2.0, 95% CI 1.8–2.1) and hypertension (aOR 2.5, 95% CI 2.4–2.6). Conclusions Among 134 209 inpatients with COVID-19, mortality was more frequent among patients with obesity and diabetes. IMV was more frequently necessary for inpatients with obesity, diabetes and hypertension. Patients for whom these were incident co-morbidities were particularly at risk. Specific medical monitoring and vaccination should be priorities for patients with these co-morbidities.

We describe a rare case of severe disseminated monkeypox (MPox) virus infection complicated by peritonitis in a 44-year-old man living with well-controlled HIV. The patient was successfully treated with tecovirimat without requiring surgery. MPox should be considered in the differential diagnosis of non-bacterial peritonitis in patients at risk of infection.

Clindamycin is an antibiotic with high bioavailability and appropriate bone diffusion, often proposed as an alternative in guidelines forA retrospective analysis was conducted at the University Hospital of Nice (France) between 2010 and 2019. We included patients with one shoulder implant surgical procedure and at least oneForty-eight SIJI were identified and 33 were treated with clindamycin, among which 25 were treated with monotherapy. The median duration of clindamycin antibiotherapy was 6 weeks. The average follow-up was 45 months; one patient was lost to follow-up. Twenty-seven patients out of 33 (82%) were cured with clindamycin, compared to 9/12 (75%) with other antibiotics. The rate of favorable outcomes increased to 27/31 (87%) with clindamycin and to 9/10 (90%) for other antibiotics when no septic revision strategies were excluded (The therapeutic strategy based on one- or two-stage revision associated with 6 weeks of clindamycin seems to be effective.

ObjectivesWe evaluated the clinical, virological and safety outcomes of lopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a, hydroxychloroquine or remdesivir in comparison to standard of care (control) in COVID-19 inpatients requiring oxygen and/or ventilatory support. While preliminary results were previously published, we present here the final results, following completion of the data monitoring.MethodsWe conducted a phase 3 multi-centre open-label, randomized 1:1:1:1:1, adaptive, controlled trial (DisCoVeRy), add-on trial to Solidarity (NCT04315948, EudraCT2020-000936-23). The primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens, pharmacokinetic and safety analyses. We report the results for the lopinavir/ritonavir-containing arms and for the hydroxychloroquine arm, which were stopped prematurely.ResultsThe intention-to-treat population included 593 participants (lopinavir/ritonavir, n=147; lopinavir/ritonavir-IFN-β-1a, n=147; hydroxychloroquine, n=150; control, n=149), among whom 421 (71.0%) were male, the median age was 64 years (IQR, 54-71) and 214 (36.1%) had a severe disease. The day 15 clinical status was not improved with investigational treatments: lopinavir/ritonavir versus control, adjusted odds ratio (aOR) 0.82, (95% confidence interval [CI] 0.54-1.25, P=0.36); lopinavir/ritonavir-IFN-β-1a versus control, aOR 0.69 (95%CI 0.45-1.05, P=0.08); hydroxychloroquine versus control, aOR 0.94 (95%CI 0.62-1.41, P=0.76). No significant effect of investigational treatment was observed on SARS-CoV-2 clearance. Trough plasma concentrations of lopinavir and ritonavir were higher than those expected, while those of hydroxychloroquine were those expected with the dosing regimen. The occurrence of Serious Adverse Events was significantly higher in participants allocated to the lopinavir/ritonavir-containing arms.ConclusionIn adults hospitalized for COVID-19, lopinavir/ritonavir, lopinavir/ritonavir-IFN-ß-1a and hydroxychloroquine did not improve the clinical status at day 15, nor SARS-CoV-2 clearance in respiratory tract specimens.

Objective We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. Methods In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. Results Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference—21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). Conclusion This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

Objectives The aim was to evaluate the feasibility and diagnostic contribution of protein profiling using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) applied to sputum to diagnose pulmonary tuberculosis. Methods Sputum samples collected from patients suspected of having pulmonary tuberculosis were analysed using MALDI-TOF MS. Using the differentially expressed protein peaks, we compared three groups of patients, including those with confirmed pulmonary tuberculosis (PTB), those without tuberculosis but with a lower respiratory tract infection (non-TB LRTI) and those without tuberculosis and without an LRTI (non-TB controls). Results A total of 102 patients included 35 PTB, 36 non-TB LRTI and 31 non-TB controls. The model differentiated between the PTB patients and the non-TB controls using the 25 most differentially expressed protein peaks, with a sensitivity of 97%, 95% CI 85–100%, and a specificity of 77%, 95% CI 59–90%. The model distinguished the PTB patients from the non-TB LRTI patients using the ten most differentially expressed protein peaks, with a sensitivity of 80%, 95% CI 63–92%, and a specificity of 89%, 95% CI 74–97%. We observed that the negative predictive value of MALDI-TOF MS sputum analysis was higher (96%, 95% CI 80–100%) than that of direct sputum microscopic examination and sputum culture (78%, 95% CI 62–89%) for non-TB controls. When MALDI-TOF MS sputum analysis and direct microscopic examination were combined, the negative predictive value reached 94%, 95% CI 80–99%, for non-TB LRTI patients. Discussion These results suggest that MALDI-TOF MS sputum analysis coupled with microscopic examination could be used as a screening tool for diagnosing pulmonary TB.