The Impact of Surgical Strategy and Rifampin on Treatment Outcome in Cutibacterium Periprosthetic Joint Infections.

BACKGROUND: Cutibacterium species are common pathogens in periprosthetic joint infections (PJI). These infections are often treated with ß-lactams or clindamycin as monotherapy, or in combination with rifampin. Clinical evidence supporting the value of adding rifampin for treatment of Cutibacterium PJI is lacking. METHODS: In this multicenter retrospective study, we evaluated patients with Cutibacterium PJI and a minimal follow-up of 12 months. The primary endpoint was clinical success, defined by the absence of infection relapse or new infection. We used Fisher's exact tests and Cox proportional hazards models to analyze the effect of rifampin and other factors on clinical success after PJI. RESULTS: We included 187 patients (72.2% male, median age 67 years) with a median follow-up of 36 months. The surgical intervention was a 2-stage exchange in 95 (50.8%), 1-stage exchange in 51 (27.3%), debridement and implant retention (DAIR) in 34 (18.2%), and explantation without reimplantation in 7 (3.7%) patients. Rifampin was included in the antibiotic regimen in 81 (43.3%) cases. Infection relapse occurred in 28 (15.0%), and new infection in 13 (7.0%) cases. In the time-to-event analysis, DAIR (adjusted hazard ratio [HR] = 2.15, P = .03) and antibiotic treatment over 6 weeks (adjusted HR = 0.29, P = .0002) significantly influenced treatment failure. We observed a tentative evidence for a beneficial effect of adding rifampin to the antibiotic treatment-though not statistically significant for treatment failure (adjusted HR = 0.5, P = .07) and not for relapses (adjusted HR = 0.5, P = .10). CONCLUSIONS: We conclude that a rifampin combination is not markedly superior in Cutibacterium PJI, but a dedicated prospective multicenter study is needed.

Patients with Long COVID continue to experience significant symptoms at 12 months and factors associated with improvement: A prospective cohort study in France (PERSICOR).

OBJECTIVES: This study examines long COVID symptoms course over 12 months, their impact on daily life, and associated factors for symptom relief. METHODS: A prospective cohort study included 231 participants with long COVID at 12-month follow-up. Data on characteristics, symptom course, and remission were collected using a questionnaire and a remission scale. Poisson regression models were used to estimate the prevalence rate ratio (PRR) and 95% confidence intervals (CIs) for factors associated with symptom improvement. RESULTS: Of the 231 participants, 63.2% developed SARS-CoV-2 antibodies before COVID-19 vaccination. At 12 months, only 8.7% (95% CI: 5.4-13.1%) reported complete remission, while 28.6% noted significant improvement. Most symptoms remained prevalent: asthenia (83.1%), neurocognitive/neurological (93.9%), cardiothoracic (77.9%), Musculoskeletal (78.8%). During long COVID, 62.2% stopped working, and only 32.5% resumed full-time professional activities. Presence of SARS-CoV-2 antibodies before vaccination increased the probability of improvement (aPRR: 1.60, P = 0.028), while ageusia at initial long COVID phase decreased the probability (aPRR: 0.38, P = 0.007). CONCLUSIONS: Long-COVID symptoms persisted in the majority of participants after 12 months, with significant impacts on daily life and work. SARS-CoV-2 antibodies were associated with better prognosis, while persistent ageusia indicated a lower probability of improvement. These findings highlight the need for ongoing support and care for individuals with long COVID.

Local budesonide therapy in the management of persistent hyposmia in suspected non-severe COVID-19 patients: Results of a randomized controlled trial.

OBJECTIVES: Consequences of COVID-19 on olfactory functions remained unclear during the pandemic. We assessed the efficacy of local budesonide in addition to olfactory rehabilitation when managing non-severe COVID-19 patients with persistent hyposmia. METHODS: A multicentric, randomized, superiority trial was conducted (ClinicalTrials.gov NCT04361474). The experimental group (EG) received budesonide and physiological saline nasal irrigations administered via three syringes of 20 ml in each nasal cavity in the morning and evening for 30 days. The control group (CG) received a similar protocol without budesonide. Patients were included if they were >18 years old, with a SARS-CoV-2 infection and presenting an isolated hyposmia persisting 30 days after symptom onset. The primary endpoint was the percentage of patients with improvement of more than two points on the ODORATEST score after 30 days of treatment. RESULTS: In total, 123 patients were included and randomized (EG: 62 vs CG: 61). Two patients from the EG met the primary endpoint with no statistical difference between the two groups (P = 0.5). CONCLUSION: To our knowledge, this is the first study evaluating local budesonide for COVID-19 related hyposmia treatment even though previous trials were performed with other local corticosteroids. Local budesonide efficacy was not demonstrated for persistent hyposmia related to COVID-19.

Divergent adaptive immune responses define two types of long COVID.

Background: The role of adaptive immune responses in long COVID remains poorly understood, with contrasting hypotheses suggesting either an insufficient antiviral response or an excessive immune response associated with inflammatory damage. To address this issue, we set to characterize humoral and CD4+ T cell responses in long COVID patients prior to SARS-CoV-2 vaccination. Methods: Long COVID patients who were seropositive (LC+, n=28) or seronegative (LC-, n=23) by spike ELISA assay were recruited based on (i) an initial SARS-CoV-2 infection documented by PCR or the conjunction of three major signs of COVID-19 and (ii) the persistence or resurgence of at least 3 symptoms for over 3 months. They were compared to COVID patients with resolved symptoms (RE, n=29) and uninfected control individuals (HD, n=29). Results: The spectrum of persistent symptoms proved similar in both long COVID groups, with a trend for a higher number of symptoms in the seronegative group (median=6 vs 4.5; P=0.01). The use a highly sensitive S-flow assay enabled the detection of low levels of SARS-CoV-2 spike-specific IgG in 22.7% of ELISA-seronegative long COVID (LC-) patients. In contrast, spike-specific IgG levels were uniformly high in the LC+ and RE groups. Multiplexed antibody analyses to 30 different viral antigens showed that LC- patients had defective antibody responses to all SARS-CoV-2 proteins tested but had in most cases preserved responses to other viruses. A sensitive primary T cell line assay revealed low but detectable SARS-CoV-2-specific CD4 responses in 39.1% of LC- patients, while response frequencies were high in the LC+ and RE groups. Correlation analyses showed overall strong associations between humoral and cellular responses, with exceptions in the LC- group. Conclusions: These findings provide evidence for two major types of antiviral immune responses in long COVID. Seropositive patients showed coordinated cellular and humoral responses at least as high as those of recovered patients. In contrast, ELISA-seronegative long COVID patients showed overall low antiviral responses, with detectable specific CD4+ T cells and/or antibodies in close to half of patients (52.2%). These divergent findings in patients sharing a comparable spectrum of persistent symptoms raise the possibility of multiple etiologies in long COVID.

Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients.

Several disabling symptoms potentially related to dysautonomia have been reported in "long-COVID" patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31-43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0-16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.

Neurological manifestations following cured malaria: don't forget post-malaria neurological syndrome.

INTRODUCTION: Cerebral malaria which occurs during the active infection is the most common neurological complication of malaria. Other complications including post-malaria neurological syndrome (PMNS) can rarely occur following complete recovery from the disease. We report a case of post-malaria neurological syndrome in a Tunisian patient. CASE PRESENTATION: A 26-year-old Tunisian man with no past medical history was admitted in 2016 for a muscle weakness of the 4 limbs, seizures, tetraparesis and myoclonus which appeared after he returned from Côte d'Ivoire where he had been treated three weeks ago for Plasmodium falciparum malaria with favorable outcome. Blood smears for malaria were negative. Brain MRI showed multiple hypersignal cerebral lesions. Investigations didn't show any infectious, metabolic, toxic, vascular or tumoral etiology. Thus, the diagnosis of PMNS was considered. The patient was treated with methylprednisolone with favorable outcome. Two years later, he was completely asymptomatic. CONCLUSION: PMNS should be considered in patients with neurological symptoms occurring within two months of cured acute disease in which blood smears for malaria are negative and other etiologies have been ruled out. In most cases, the disease is self-limited while in severe cases corticosteroid therapy should be prescribed with favorable outcome.

Asymptomatic SARS COV-2 carriers among nursing home staff: A source of contamination for residents?

OBJECTIVES: To show that circulation of SARS-COV-2 in nursing homes in France can come from staff as well as residents' families, whether they are known or not to have had COVID-19. METHODS: This study reports a screening campaign of asymptomatic staff working in elderly nursing homes in Paris where the virus had been circulating actively in March and April 2020. RESULTS: Before the screening campaign, the rate of symptomatic COVID-19 was 23.3% among the residents and 12.1% among their home employees. Within a 72 h screening period, all employees not known to have the virus were screened by RT-PCR in nasopharyngeal swabs. Among the 241 screened employees, 32 (13.3%) tested positive for SARS-CoV-2 on RT-PCR. SARS-CoV-2 carriers and non-carriers did not differ in term of gender, age or type of staff. Staff carrying SARS-CoV-2 were strictly asymptomatic in 75% of cases while during the days following or before the test, 25% presented mild symptoms of COVID-19. Considering both symptomatic and asymptomatic cases, 66 out of 281 (23.5%) of the home employees had been carriers for COVID-19. CONCLUSION: Screening for viral carriage of asymptomatic staff in nursing homes can avoid contact and transmission to frequently severely vulnerable residents.

Efficacy of local budesonide therapy in the management of persistent hyposmia in COVID-19 patients without signs of severity: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the efficacy of local intranasal treatment with budesonide (nasal irrigation), in addition to olfactory rehabilitation, in the management of loss of smell in COVID-19 patients without signs of severity and with persistent hyposmia 30 days after the onset of symptoms. To search for an association between the presence of an obstruction on MRI and the severity of olfactory loss, at inclusion and after 30 days of treatment. TRIAL DESIGN: Two center, open-label, 2-arm (1:1 ratio) parallel group randomized controlled superiority trial. PARTICIPANTS: Inclusion criteria - Patient over 18 years of age; - Patient with a suspected SARS-CoV-2 infection, whether or not confirmed by PCR, or close contact with a PCR-confirmed case, typical chest CT scan (unsystematic frosted glass patches with predominantly sub-pleural appearance, and at a later stage, alveolar condensation without excavation or nodules or masses) or positive serology ; - Patient with isolated sudden onset hyposmia persisting 30 days after the onset of symptoms of CoV-2 SARS infection; - Affiliate or beneficiary of a social security scheme; - Written consent to participate in the study. Non-inclusion criteria - Known hypersensitivity to budesonide or any of the excipients; - Hemostasis disorder or epistaxis; - Oral-nasal and ophthalmic herpes virus infection; - Long-term corticosteroid treatment; - Treatment with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone and HIV protease inhibitors); - Severe forms of SARS-CoV-2 with respiratory or other signs; - Hyposmia persisting for more than 90 days after the onset of symptoms - Other causes of hyposmia found on interrogation or MRI; - Patient benefiting from a legal protection measure; - Pregnant or breastfeeding women. The participants will be recruited from: Hôpital Fondation Adolphe de Rothschild and Hôpital Lariboisière in Paris, France INTERVENTION AND COMPARATOR: Intervention: Experimental group: Nasal irrigation with budesonide and physiological saline (Budesonide 1mg/2mL diluted in 250mL of physiological saline 9°/00): 3 syringes of 20mL in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. CONTROL GROUP: Nasal irrigation with physiological saline 9°/00 only: 3 syringes of 20cc in each nasal cavity, morning and evening, for 30 days, in addition to olfactory rehabilitation twice a day. MAIN OUTCOMES: Percentage of patients with an improvement of more than 2 points on the ODORATEST score after 30 days of treatment. RANDOMISATION: Patients will be randomized (1:1) between the experimental and control groups, using the e-CRF. The randomization list will be stratified by centre. BLINDING (MASKING): Participants and caregivers are aware of the group assignment. People assessing the outcomes are blinded to the group assignment Numbers to be randomised (sample size) 120 patients are planned to be randomized into two groups of 60 patients. TRIAL STATUS: MDL_2020_10. Version number 2, May 22, 2020. Recruitment started on May 22, 2020. The trial will finish recruiting by August 2020. TRIAL REGISTRATION: EUDRACT number: 2020-001667-85; date of trial registration: 15 May 2020 Protocol registered on ClinicalTrial.gov, registration number: NCT04361474 ; date of trial registration: 24 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

HIV infection and COVID-19: risk factors for severe disease.

: We performed an observational prospective monocentric study in patients living with HIV (PLWH) diagnosed with COVID-19. Fifty-four PLWH developed COVID-19 with 14 severe (25.9%) and five critical cases (9.3%), respectively. By multivariate analysis, age, male sex, ethnic origin from sub-Saharan Africa and metabolic disorder were associated with severe or critical forms of COVID-19. Prior CD4 T cell counts did not differ between groups. No protective effect of a particular antiretroviral class was observed.

Clinical recurrences of COVID-19 symptoms after recovery: Viral relapse, reinfection or inflammatory rebound?

For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.

Self-reported loss of smell without nasal obstruction to identify COVID-19. The multicenter Coranosmia cohort study.

OBJECTIVES: To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (<7 days) loss of smell and to assess the diagnostic accuracy of olfactory/gustatory dysfunction for COVID-19 diagnosis in the overall population tested for COVID-19 in the same period. METHODS: Prospective multicentric cohort study in four olfactory ENT units and a screening center for COVID-19. RESULTS: i) Among a subset of 55 patients consulting for primarily recent loss of smell, we found that 51 (92.7%) had a COVID-19 positive test (median viral load of 28.8 cycle threshold). Loss of smell was mostly total (anosmia), rarely associated with nasal obstruction but associated with a taste disorder in 80%. Olfactory dysfunction occurred suddenly, either as first complaint or preceded by mild symptoms occurring a median of 3 days. The majority of patients (72.9%) partially recovered the sense of smell within 15 days. ii) In a population of 1824 patients tested for COVID-19, the positive predictive value and the specificity of loss of smell and/or taste were 78.5% and 90.3% respectively (sensitivity (40.8%), negative predictive value (63.6%)). CONCLUSIONS: Self-reported loss of smell had a high predictive positive value to identify COVID-19. Making this sign well known publicly could help to adopt isolation measures and inform potential contacts.

Cerebral Vasculitis Complicating Pneumococcal Meningitis.

INTRODUCTION: Cerebral vasculitis is an uncommon life-threatening complication of community-acquired bacterial meningitis. PATIENT AND METHODS: We report the case of a 64-year-old woman with pneumococcal meningitis who developed parainfectious vasculitis causing ischaemic brain damage. Cerebral magnetic resonance imaging (MRI) confirmed the diagnosis. Clinical and radiological recovery after delayed addition of corticosteroid was achieved. DISCUSSION: This report shows that the onset of neurological deficits following pneumococcal meningitis can be caused by cerebral vasculitis. Underdosing with antibiotics and delayed adjunctive dexamethasone seem to favour this complication. There are no guidelines for treatment but high doses of steroids led to resolution in this case. LEARNING POINTS: Pneumococcal meningitis complicated by cerebral vasculitis can be treated with high-dose steroids.A repeat lumbar puncture is recommended to rule out relapsing or persistent infection in patients who deteriorate after 48 h of adequate antibiotic therapy.The cerebral vasculitis in our patient may have been caused by antibiotic underdosing and by delayed dexamethasone administration.