Modeling SARS-CoV-2 viral kinetics and association with mortality in hospitalized patients from the French COVID cohort.

The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (P < 10-4). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio [HR] > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31, P < 10-3). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.

Positive intrathecal anti-Borrelia antibody synthesis: what are the implications for clinical practice? Clinical features and outcomes of 138 patients in a French multicenter cohort study.

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.

Staphylococcus aureus Genomic Analysis and Outcomes in Patients with Bone and Joint Infections: A Systematic Review.

Many studies have been published assessing the association between the presence of S. aureus genes and outcomes in patients with bone and joint infections (BJI), but it is not known if they have had similar findings. A systematic literature review was performed. All available data on studies in Pubmed between January 2000 to October 2022 reporting the genetic characteristics of S. aureus and the outcomes of BJIs were analyzed. BJI included prosthetic joint infection (PJI), osteomyelitis (OM), diabetic foot infection (DFI), and septic arthritis. Because of the heterogeneity of studies and outcomes, no meta-analysis was performed. With the search strategy, 34 articles were included: 15 articles on children and 19 articles on adults. In children, most BJI studied were OM (n = 13) and septic arthritis (n = 9). Panton Valentine leucocidin (PVL) genes were associated with higher biological inflammatory markers at presentation (n = 4 studies), more febrile days (n = 3), and more complicated/severe infection (n = 4). Other genes were reported anecdotally associated with poor outcomes. In adults, six studies reported outcomes in patients with PJI, 2 with DFI, 3 with OM, and 3 with various BJI. Several genes were associated with a variety of poor outcomes in adults, but studies found contradictory results. Whereas PVL genes were associated with poor outcomes in children, no specific genes were reported similarly in adults. Additional studies with homogenous BJI and larger sample sizes are needed.

BNT162b2 Messenger RNA Vaccination Did Not Prevent an Outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 Variant 501Y.V2 in an Elderly Nursing Home but Reduced Transmission and Disease Severity.

We report an outbreak of severe acute respiratory syndrome coronavirus 2 501Y.V2 in a nursing home. All nonvaccinated residents (5/5) versus half of those vaccinated with BNT162b2 (13/26) were infected. Two of 13 vaccinated versus 4 of 5 nonvaccinated residents presented severe disease. BNT162b2 did not prevent the outbreak, but reduced transmission and disease severity.

Infective endocarditis in pregnant women without intravenous drug use: a multicentre retrospective case series.

OBJECTIVES: To describe the clinical features and outcomes of infective endocarditis (IE) in pregnant women who do not inject drugs. METHODS: A multinational retrospective study was performed at 14 hospitals. All definite IE episodes between January 2000 and April 2021 were included. The main outcomes were maternal mortality and pregnancy-related complications. RESULTS: Twenty-five episodes of IE were included. Median age at IE diagnosis was 33.2 years (IQR 28.3-36.6) and median gestational age was 30 weeks (IQR 16-32). Thirteen (52%) patients had no previously known heart disease. Sixteen (64%) were native IE, 7 (28%) prosthetic and 2 (8%) cardiac implantable electronic device IE. The most common aetiologies were streptococci (n = 10, 40%), staphylococci (n = 5, 20%), HACEK group (n = 3, 12%) and Enterococcus faecalis (n = 3, 12%). Twenty (80%) patients presented at least one IE complication; the most common were heart failure (n = 13, 52%) and symptomatic embolism other than stroke (n = 4, 16%). Twenty-one (84%) patients had surgery indication and surgery was performed when indicated in 19 (90%). There was one maternal death and 16 (64%) patients presented pregnancy-related complications (11 patients ≥1 complication): 3 pregnancy losses, 9 urgent Caesarean sections, 2 emergency Caesarean sections, 1 fetal death, and 11 preterm births. Two patients presented a relapse during a median follow-up of 3.1 years (IQR 0.6-7.4). CONCLUSIONS: Strict medical surveillance of pregnant women with IE is required and must involve a multidisciplinary team including obstetricians and neonatologists. Furthermore, the potential risk of IE during pregnancy should never be underestimated in women with previously known underlying heart disease.

Olfactory dysfunction in COVID-19, new insights from a cohort of 353 patients: The ANOSVID study.

Olfactory disorders (OD) pathogenesis, underlying conditions, and prognostic in coronavirus disease 2019 (COVID-19) remain partially described. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from March 1 2020 to May 31 2020. The aim was to compare COVID-19 patients with OD (OD group) and patients without OD (no-OD group). A second analysis compared patients with anosmia (high OD group) and patients with hyposmia or no OD (low or no-OD group). The OD group presented less cardiovascular and other respiratory diseases compared to the no-OD group (odds ratio [OR] = 0.536 [0.293-0.981], p = 0.041 and OR = 0.222 [0.056-0.874], p = 0.037 respectively). Moreover, history of malignancy was less present in the high OD group compared with the low or no-OD group (OR = 0.170 [0.064-0.455], p < 0.001). The main associated symptoms (OR > 5) with OD were loss of taste (OR = 24.059 [13.474-42.959], p = 0.000) and cacosmia (OR = 5.821 [2.246-15.085], p < 0.001). Most of all ORs decreased in the second analysis, especially for general, digestive, and ENT symptoms. Only two ORs increased: headache (OR = 2.697 [1.746-4.167], p < 0.001) and facial pain (OR = 2.901 [1.441-5.842], p = 0.002). The high OD group had a higher creatinine clearance CKD than the low or no-OD group (89.0 ± 21.1 vs. 81.0 ± 20.5, p = 0.040). No significant difference was found concerning the virological, radiological, and severity criteria. OD patients seem to have less comorbidity, especially better cardiovascular and renal function. Associated symptoms with OD were mostly neurological symptoms. We did not find a significant relationship between OD and less severity in COVID-19 possibly due to methodological bias.

Older adults with SARS-CoV-2 infection: Utility of the clinical frailty scale to predict mortality.

The objective of this study was to identify predictive factors of mortality in older adults with coronavirus disease 2019 (COVID-19), including the level of clinical frailty by using the clinical frailty scale (CFS). We analyzed medical records of all patients aged of 75 and older with a confirmed diagnosis of COVID-19 hospitalized in our Hospital between March 3 and April 25, 2020. Standardized variables were prospectively collected, and standardized care were provided to all patients. One hundred and eighty-six patients were included (mean 85.3 ± 5.78 year). The all cause 30-day mortality was 30% (56/186). At admission, dead patients were more dyspneic (57% vs. 38%, p = .014), had more often an oxygen saturation less than 94% (70% vs. 47%, p < .01) and had more often a heart rate faster than 90/min (70% vs. 42%, p < .001). Mortality increased in parallel with CFS score (p = .051) (20 deaths (36%) in 7-9 category). In multivariate analysis, CFS score (odds ratio [OR] = 1.49; confidence interval [CI] 95%, 1.01-2.19; p = .046), age (OR = 1.15; CI 95%, 1.01-1.31; p = .034), and dyspnea (OR = 5.37; CI 95%, 1.33-21.68; p = .018) were associated with all-cause 30-day mortality. It is necessary to integrate the assessment of frailty to determine care management plan of older patients with COVID-19, rather than the only restrictive criterion of age.

SARS-CoV-2 respiratory viral loads and association with clinical and biological features.

To determine the distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viral loads (VL) during the acute phase of infection and their correlation with clinical presentation and inflammation-related biomarkers. Nasopharyngeal swabs from 453 adult SARS-CoV-2-infected patients from the Department of Infectious Diseases, Besançon, France, were collected at the time of admission or consultation for reverse transcriptase polymerase chain reaction (RT-PCR) analysis. Clinical information and concentrations of biological parameters (C-reactive protein [CRP], fibrinogen, lactate dehydrogenase [LDH], prealbumin) were noticed. Mean respiratory VL homogeneously decreased from 7.2 log10 copies/ml (95% confidence interval [CI]: 6.6-7.8) on the first day of symptoms until 4.6 log10 copies/ml (95% CI: 3.8-5.4) at day 10 (slope = -0.24; R2 = .95). VL were poorly correlated with COVID-19 symptoms and outcome, excepted for dyspnea and anosmia, which were significantly associated with lower VL (p < .05). CRP, fibrinogen, and LDH concentrations significantly increased over the first 10 days (median CRP concentrations from 36.8 mg/L at days 0-1 to 99.5 mg/L at days 8-10; p < .01), whereas prealbumin concentrations tended to decrease. Since SARS-CoV-2 respiratory VL regularly decrease in the acute phase of infection, determining the level of VL may help predicting the onset of virus shedding in a specific patient. However, the role of SARS-CoV-2 VL as a biomarker of severity is limited.

Epidemiology and risk factors for ureteral stent-associated urinary tract infections in non-transplanted renal patients: a systematic review of the literature.

PURPOSE: Pathophysiology and risk factors for Ureteral Stent-Associated Urinary Tract Infection (USAUTI) have been poorly investigated. This situation results in highly diverse practices regarding USAUTI prevention, diagnosis and treatment. The aim of the present study was to describe the epidemiology and risk factors for USAUTI in non-transplanted patients. METHODS: We conducted a systematic literature review based on a comprehensive PubMed® bibliographic strategy, between October 1998 and March 2020. The methodological quality of the studies included was analyzed according to dedicated grids. The main endpoints were the correlation between different potential risk factors and infection ureteral stent-associated urinary tract infection or colonization rate. Conclusions and their level of evidence were reported on the basis of a critical analysis of the best available scientific evidence. This work has been submitted to a national review, which enabled the potentially divergent opinions of experts to be collected, thereby ensuring adequate quality of data. RESULTS AND CONCLUSION: Twenty-six studies out of the 505 articles identified, were included in the final analysis. Staphylococcus spp, E. coli, Klebsiella spp, Pseudomona aeruginosa, Enterococcus spp. and Candida spp. were the microorganisms most often responsible for asymptomatic bacteriuria (ABU) or USAUTI. Longer indwelling time, diabetes mellitus, female gender, chronic renal failure, diabetic nephropathy and cancer were identified as risk factors for ABU and ureteral stent colonization. No specific risk factor for UTI was identified in the literature studied. A causal relationship between ureteral stent colonization and USAUTI or urosepsis remains to be demonstrated.

Elevated D-dimers and lack of anticoagulation predict PE in severe COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism. We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients. METHODS: Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min-1) or rapid clinical worsening. Multivariable analysis was performed using Firth penalised maximum likelihood estimates. RESULTS: 162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%). PE was diagnosed in 44 (27.2%) patients. Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%. By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively). Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL-1 to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%). D-dimer level >2590 ng·mL-1 was associated with a 17-fold increase in the adjusted risk of PE. CONCLUSION: Elevated D-dimers (>2590 ng·mL-1) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity. These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.

Risk factors and clinical characteristics of patients with nosocomial influenza A infection.

Influenza is a public health burden, responsible for more than half a million deaths worldwide each year and explosive outbreaks in-hospital care units. At present, little is known about clinical characteristics and outcomes with nosocomial influenza infection. To assess clinical characteristics and outcome between nosocomial and community-acquired (CA) influenza in a tertiary care hospital. A retrospective study of hospitalized patients in a French tertiary care hospital from 1st December 2016 to 28th February 2017 for flu-illness confirmed by reverse transcription PCR. Overall, 208 patients with laboratory-confirmed influenza were included; whose 49 nosocomial cases (23.6%). Patients with nosocomial influenza were significantly older (79.1 ± 15.5 vs 64.8 ± 31.1 years old; P = .003), with the more rapidly fatal disease (10.2% vs 1.3%; P = .0032). They had a less respiratory failure (8.2% vs 21.4%; P = .036) but had a longer length of hospitalization (47.3 vs 12.9 days; P < .001) than patients with CA influenza. During this influenza outbreak, 19 patients died (9.1%), none of them were vaccinated. Effective control of outbreaks in hospital facilities is challenging. Hospitalized patients are vulnerable to nosocomial Influenza infections that can increase the length of stay and be responsible for the death. Surveillance and early warning systems should be encouraged. Vaccination policies in conjunction with isolation measures and better hand hygiene could reduce virus spreading in hospitals.

Spread of clonal linezolid-resistant Staphylococcus epidermidis in an intensive care unit associated with linezolid exposure.

The aim of the study was to determine factors associated with spread of linezolid (LNZ)-resistant Staphylococcus epidermidis isolates in a surgical intensive care unit (ICU). A case-control study was conducted in one French adult surgical ICU. From January 2012 to December 2016, patients with at least a single positive LNZ-resistant S. epidermidis blood culture were matched to control with LNZ-susceptible S. epidermidis blood culture in a 1:4 manner. Cases were compared to controls regarding baseline clinical characteristics and LNZ exposure before positive blood culture. Bacterial isolates were genotyped by using pulsed-field gel electrophoresis (PFGE) and MLST. We identified 13 LNZ-resistant S. epidermidis isolates, 1 in 2012, 3 in 2014, 6 in 2015, and 3 in 2016. LNZ use increased steadily from 8 DDDs/100 patient days in 2010 to 19 in 2013 and further decrease by more of 50% in 2015 and 2016. The only independent risk factors associated to LNZ-resistant S. epidermidis isolation were length of stay in ICU before infection (OR 1.45; 95% CI 1.07-1.98), prior exposure to LNZ (OR 109; 95% CI 3.9-3034), and Charlson comorbidities score (OR 3.19; 95% CI 1.11-9.14). PFGE typing showed that all LNZ-resistant isolates were clonal belonging to ST2 and that LNZ-susceptible isolates were highly diverse. We report herein that previous exposure to LNZ substantially increased the risk of occurrence of LNZ resistance in S. epidermidis even in the case of clonal spread of LNZ-resistant isolates. These findings highlight the need for reducing the use of LNZ to preserve its efficacy in the future.

Utility of CT scan in patients with initial negative PCR for SARS-CoV2: a report of three cases.

PCR-based viral RNA to confirm the diagnosis of SARS-CoV-2 infection has a sensitivity of around 70%. We report three cases of patients with negative initial PCR and CT scan lesions that led us to suspect COVID-19, but which one(s) are really COVID-19?

Epidemiology and risk factors of Staphylococcus aureus CC398 bone and joint infections.

BACKGROUND: A particular ability of the Staphylococcus aureus clonal complex 398 (CC398) to cause bone and joint infections (BJI) remains questionable, since some studies have described high prevalence of MSSA CC398 in prosthetic joint infection (PJI) and diabetic foot ostemolyelitis (DFO). Here, we described the long-term epidemiology of CC398 among S. aureus isolated from BJI and identified risk factors associated with CC398. METHODS: We included all bone and joint samples with S. aureus-positive culture in our university hospital between January 2010 and December 2017. Logistic regression was used for univariate and multivariate analysis. RESULTS: We identified 124 CC398 isolates among the 958 BJI-associated S. aureus. The proportion of CC398 among S. aureus increased steadily from 4% in 2010 to 26% in 2017. Only 4 isolates of CC398 were resistant to methicillin. The distribution of BJI types due to CC398 and non CC398 isolates was similar. In multivariate analysis, age (p = 0.034, OR = 3.9), McCabe score (p = 0.005, OR = 5) and inoculation mechanism (p = 0.020, OR = 3.7) were associated with PJI-related CC398. The year of infection (p < 0.001, OR = 1.6), Charlson's score (p = 0.001, OR = 1.5) and grade 4 (severe) of the International Working Group of the Diabetic Foot classification (p < 0.001, OR = 8.5) were associated with DFO-related CC398. CONCLUSION: We highlighted here the emergence and spread of CC398-MSSA in BJI. Patients with comorbidities are at high risk of CC398 MSSA PJI and DFO. The spread of CC398 in the community and hospital settings remains unclear and further epidemiological studies are needed to identify the determinants of its success.

COVID-19 outbreak: organisation of a geriatric assessment and coordination unit. A French example.

Older people are particularly affected by the COVID-19 outbreak because of their vulnerability as well as the complexity of health organisations, particularly in the often-compartmentalised interactions between community, hospital and nursing home actors. In this endemic situation, with massive flows of patients requiring holistic management including specific and intensive care, the appropriate assessment of each patient's level of care and the organisation of specific networks is essential. To that end, we propose here a territorial organisation of health care, favouring communication between all actors. This organisation of care is based on three key points: To use the basis of territorial organisation of health by facilitating the link between hospital settings and geriatric sectors at the regional level.To connect private, medico-social and hospital actors through a dedicated centralised unit for evaluation, geriatric coordination of care and decision support. A geriatrician coordinates this multidisciplinary unit. It includes an emergency room doctor, a supervisor from the medical regulation centre (Centre 15), an infectious disease physician, a medical hygienist and a palliative care specialist.To organise an ad hoc follow-up channel, including the necessary resources for the different levels of care required, according to the resources of the territorial network, and the creation of a specific COVID geriatric palliative care service. This organisation meets the urgent health needs of all stakeholders, facilitating its deployment and allows the sustainable implementation of a coordinated geriatric management dynamic between the stakeholders on the territory.

Increasing incidence of bloodstream infections due to Staphylococcus aureus clonal complex 398 in a French hospital between 2010 and 2017.

The epidemiology of Staphylococcus aureus is changing and several surveillances worldwide have evidenced an increasing incidence of S. aureus bloodstream infections (BSIs). Here, we described the long-term epidemiology of the emergent clonal group CC398 among S. aureus isolated from BSIs in our French university hospital between 2010 and 2017. Each patient with at least one blood culture positive with S. aureus during the study period was included (N = 1455). Cefoxitin susceptibility was determined using the disk diffusion method according to EUCAST recommendations. CC398 isolates were first screened from the whole S. aureus collection with a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) typing method confirmed by a CC398-specific PCR. In our hospital, the incidence of hospital- and community-acquired BSIs due to S. aureus and MSSA increased in parallel between 2010 and 2017 while that of BSIs with MRSA decreased. The prevalence of CC398 isolates among S. aureus from BSIs increased from 3.6 in 2010 to 20.2% in 2017 (p < 0.05). CC398-MRSA emerged but remains very sparse. Our data suggested that CC398-MSSA disseminates in the community. We showed here the emergence and the diffusion of CC398-MSSA, a subclone associated with invasive infections, in our hospital. The monitoring of this particular human-adapted S. aureus clone is needed and genomic studies will have to identify the determinants of its diffusion.

A comparison of TAFRO syndrome between Japanese and non-Japanese cases: a case report and literature review.

TAFRO syndrome was first described as a variant of multicentric Castleman's disease with thrombocytopenia, anasarca, fever, renal dysfunction, and organomegaly. We report the case of a 25-year-old Caucasian male with diagnosis of TAFRO syndrome and present a literature review. The objective of the study was to compare TAFRO syndrome between Japanese and non-Japanese patients. Cases were included by searching the term "TAFRO" in the Medline database using PubMed between 2010 and 2016. The Student t test and Mann-Whitney U test were used to compare continuous variables. Fisher's exact test was used for categorical variables. Statistical significance was set at p < 0.05. Forty-four cases were included. Thirty-two patients (73%) were of Japanese origin. Japanese patients were significantly older than non-Japanese ones (52.0 ± 13.6 years versus 36.9 ± 19.8 years, p = 0.0064) but there was no difference in gender. Creatinine level on admission was significantly higher in the non-Japanese group (1.87 ± 0.84 mg/dL versus 1.32 ± 0.57 mg/dL, p = 0.0347). There were no significant differences concerning lymphadenopathy, elevated number of megakaryocytes on bone marrow aspiration, autoimmune abnormalities, and the following parameters on admission: platelet count, hemoglobin, albumin, alkaline phosphatase (ALP). Corticotherapy was always used on induction for Japanese patients while it was only used in 75% of the cases on induction in non-Japanese patients (p = 0.0166). Our study was the first to compare TAFRO syndrome according to ethnicity. Japanese patients were significantly older and had a significantly lower creatinine level on admission than non-Japanese patients.