Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase.

Encephalitis is a rare and potentially fatal manifestation of herpes simplex type 1 infection. Following genome-wide genetic analyses, we identified a previously uncharacterized and very rare heterozygous variant in the E3 ubiquitin ligase WWP2, in a 14-month-old girl with herpes simplex encephalitis. The p.R841H variant (NM_007014.4:c.2522G > A) impaired TLR3 mediated signaling in inducible pluripotent stem cells-derived neural precursor cells and neurons; cells bearing this mutation were also more susceptible to HSV-1 infection compared to control cells. The p.R841H variant increased TRIF ubiquitination in vitro. Antiviral immunity was rescued following the correction of p.R841H by CRISPR-Cas9 technology. Moreover, the introduction of p.R841H in wild type cells reduced such immunity, suggesting that this mutation is linked to the observed phenotypes.

Investigations of an increased incidence of non-Aspergillus invasive mould infections in an onco-haematology unit.

AIMS OF THE STUDY: Invasive mould infections are life-threatening complications in patients with haematologic cancer and chemotherapy-induced neutropenia. While invasive aspergillosis represents the main cause of invasive mould infections, non-Aspergillus mould infections, such as mucormycosis, are increasingly reported. Consequently, their local epidemiology should be closely monitored. The aim of this study was to investigate the causes of an increased incidence of non-Aspergillus mould infections in the onco-haematology unit of a Swiss tertiary care hospital. METHODS: All cases of proven and probable invasive mould infections were retrospectively identified via a local registry for the period 2007-2021 and their incidence was calculated per 10,000 patient-days per year. The relative proportion of invasive aspergillosis and non-Aspergillus mould infections was assessed. Factors that may affect invasive mould infections' incidence, such as antifungal drug consumption, environmental contamination and changes in diagnostic approaches, were investigated. RESULTS: A significant increase of the incidence of non-Aspergillus mould infections (mainly mucormycosis) was observed from 2017 onwards (Mann and Kendall test p = 0.0053), peaking in 2020 (8.62 episodes per 10,000 patient-days). The incidence of invasive aspergillosis remained stable across the period of observation. The proportion of non-Aspergillus mould infections increased significantly from 2017 (33% vs 16.8% for the periods 2017-2021 and 2007-2016, respectively, p = 0.02). Building projects on the hospital site were identified as possible contributors of this increase in non-Aspergillus mould infections. However, novel diagnostic procedures may have improved their detection. CONCLUSIONS: We report a significant increase in non-Aspergillus mould infections, and mainly in mucormycosis infections, since 2017. There seems to be a multifactorial origin to this increase. Epidemiological trends of invasive mould infections should be carefully monitored in onco-haematology units in order to implement potential corrective measures.

Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study.

Respiratory viral infections (RVIs) are common reasons for healthcare consultations. The inpatient management of RVIs consumes significant resources. From 2009 to 2014, we assessed the costs of RVI management in 4776 hospitalized children aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by detailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU ('non-ICU') versus management requiring ICU care ('ICU') added up to EUR 2767.14 (non-ICU) vs. EUR 29,941.71 (ICU) for influenza, EUR 2713.14 (non-ICU) vs. EUR 16,951.06 (ICU) for RSV infections, and EUR 2767.33 (non-ICU) vs. EUR 14,394.02 (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all eight RVIs studied: influenza, RSV, hRV, adenovirus (hAdV), metapneumovirus (hMPV), parainfluenza virus (hPIV), bocavirus (hBoV), and seasonal coronavirus (hCoV) infections. ICU costs for influenza, however, exceeded all other RVIs. At the time of the study, influenza was the only RVI with antiviral treatment options available for children, but only 9.8% of influenza patients (non-ICU) and 1.5% of ICU patients with influenza received antivirals; only 2.9% were vaccinated. Future studies should investigate the economic impact of treatment and prevention of influenza, COVID-19, and RSV post vaccine introduction.

Tularemia on the rise in Switzerland? A one health approach is needed!

In the last 10 years, an increase in tularemia cases has been observed in both humans and animals in Switzerland. In these, infection with Francisella tularensis, the causative agent of the zoonotic disease tularemia, can occur through arthropod vectors or contact to infected animals or exposure to contaminated environmental sources. Currently, we are only able to postulate potential aetiologies: (i) behavioral changes of humans with more exposure to endemic habitats of infected arthropod vectors; (ii) an increased rate of tularemia infected ticks; (iii) increasing number and geographical regions of tick biotopes; (iv) increasing and/or more diverse reservoir populations; (v) increasing presence of bacteria in the environment; (vi) raised awareness and increased testing among physicians; (vii) improved laboratory techniques including molecular testing. To approach these questions, a one-health strategy is necessary. A functioning collaboration between public health, human medicine, and diagnostic and veterinary units for the control of tularemia must be established. Furthermore, the public should be included within citizen-supported-science-projects.

Chlamydia pneumoniae Upsurge at Tertiary Hospital, Lausanne, Switzerland.

Chlamydia pneumoniae infection cases have usually accounted for <1.5% of community-acquired respiratory tract infections. Currently, Lausanne, Switzerland is experiencing a notable upsurge in cases, with 28 reported within a span of a few months. This upsurge in cases highlights the need for heightened awareness among clinicians.

Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multifaceted disease potentially responsible for various clinical manifestations including gastro-intestinal symptoms. Several evidences suggest that the intestine is a critical site of immune cell development, gut microbiota could therefore play a key role in lung immune response. We designed a monocentric longitudinal observational study to describe the gut microbiota profile in COVID-19 patients and compare it to a pre-existing cohort of ventilated non-COVID-19 patients. METHODS: From March to December 2020, we included patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample. 16S metagenomics was performed on rectal swabs from these 57 COVID-19 patients, 35 with one and 22 with multiple stool collections. Nineteen non-COVID-19 ICU controls were also enrolled, among which 14 developed ventilator-associated pneumonia (pneumonia group) and five remained without infection (control group). SARS-CoV-2 viral loads in fecal samples were measured by qPCR. RESULTS: Although similar at inclusion, Shannon alpha diversity appeared significantly lower in COVID-19 and pneumonia groups than in the control group at day 7. Furthermore, the microbiota composition became distinct between COVID-19 and non-COVID-19 groups. The fecal microbiota of COVID-19 patients was characterized by increased Bacteroides and the pneumonia group by Prevotella. In a distance-based redundancy analysis, only COVID-19 presented significant effects on the microbiota composition. Moreover, patients in ICU harbored increased Campylobacter and decreased butyrate-producing bacteria, such as Lachnospiraceae, Roseburia and Faecalibacterium as compared to patients in medicine. Both the stay in ICU and patient were significant factors affecting the microbiota composition. SARS-CoV-2 viral loads were higher in ICU than in non-ICU patients. CONCLUSIONS: Overall, we identified distinct characteristics of the gut microbiota in COVID-19 patients compared to control groups. COVID-19 patients were primarily characterized by increased Bacteroides and decreased Prevotella. Moreover, disease severity showed a negative correlation with butyrate-producing bacteria. These features could offer valuable insights into potential targets for modulating the host response through the microbiota and contribute to a better understanding of the disease's pathophysiology. TRIAL REGISTRATION: CER-VD 2020-00755 (05.05.2020) & 2017-01820 (08.06.2018).

Nanomotion technology in combination with machine learning: a new approach for a rapid antibiotic susceptibility test for Mycobacterium tuberculosis.

Nanomotion technology is a growth-independent approach that can be used to detect and record the vibrations of bacteria attached to cantilevers. We have developed a nanomotion-based antibiotic susceptibility test (AST) protocol for Mycobacterium tuberculosis (MTB). The protocol was used to predict strain phenotype towards isoniazid (INH) and rifampicin (RIF) using a leave-one-out cross-validation (LOOCV) and machine learning techniques. This MTB-nanomotion protocol takes 21 h, including cell suspension preparation, optimized bacterial attachment to functionalized cantilever, and nanomotion recording before and after antibiotic exposure. We applied this protocol to MTB isolates (n = 40) and were able to discriminate between susceptible and resistant strains for INH and RIF with a maximum sensitivity of 97.4% and 100%, respectively, and a maximum specificity of 100% for both antibiotics when considering each nanomotion recording to be a distinct experiment. Grouping recordings as triplicates based on source isolate improved sensitivity and specificity to 100% for both antibiotics. Nanomotion technology can potentially reduce time-to-result significantly compared to the days and weeks currently needed for current phenotypic ASTs for MTB. It can further be extended to other anti-TB drugs to help guide more effective TB treatment.

Rectal shedding of monkeypox virus in a patient coinfected with Chlamydia trachomatis and Neisseria gonorrhoeae: a case report.

BACKGROUND: Infection by the monkeypox virus classically causes a cutaneous rash that is preceded by fever and lymph node swelling, as well as other nonspecific systemic symptoms. A recent outbreak occurred and spread in Europe and other regions, especially among patients who declare themselves as men who have sex with men. Current reports have shown that cutaneous lesions may be limited to the anogenital area. We report on a case of proctitis caused by monkeypox virus, without visible typical lesions of this virus. CASE PRESENTATION: A 29-year-old Caucasian male presented with a monkeypox virus proctitis that recurred after treatment for a documented Neisseria gonorrhoeae and Chlamydia trachomatis coinfection, likely acquired at the same time. The proctitis was preceded by fever and a swollen inguinal lymph node, and was associated with a hemorrhoid. The monkeypox virus polymerase chain reaction of a rectal swab documented high viral loads, although no typical lesion was visible. After resolution of the rectitis, the patient developed a single dermatome herpes zoster, despite the absence of usual risk factors. The patient evolved well without further specific treatment. CONCLUSION: This case shows that monkeypox virus can be responsible for proctitis, without any typical lesion, along with the important rectal shedding of the virus. It raises the concern of contagion during anal intercourse through body fluids and gives further credit that monkeypox virus can be a sexually transmitted infection. This should prompt routine rectal screening in patients with proctitis accompanied by fever and swollen lymph nodes, and in patients who have a history of unprotected receptive anal sex, even in presence of other sexually transmitted infections, and especially during a monkeypox virus outbreak. The potential link between monkeypox virus infection and shingles warrants further investigations.

Performance of microbiological tests for tuberculosis diagnostic according to the type of respiratory specimen: A 10-year retrospective study.

Background: The microbial diagnosis of tuberculosis (TB) remains challenging and relies on multiple microbiological tests performed on different clinical specimens. Polymerase chain reactions (PCRs), introduced in the last decades has had a significant impact on the diagnosis of TB. However, questions remain about the use of PCRs in combination with conventional tests for TB, namely microscopy and culture. We aimed to determine the performance of microscopy, culture and PCR for the diagnosis of pulmonary tuberculosis according to the type of clinical specimen in order to improve the diagnostic yield and to avoid unnecessary, time and labor-intensive tests. Methods: We conducted a retrospective study (2008-2018) on analysis (34'429 specimens, 14'358 patients) performed in our diagnostic laboratory located in the Lausanne University Hospital to compare the performance of microbiological tests on sputum, induced sputum, bronchial aspirate and bronchoalveolar lavage (BAL). We analysed the performance using a classical "per specimen" approach and a "per patient" approach for paired specimens collected from the same patient. Results: The overall sensitivities of microscopy, PCR and culture were 0.523 (0.489, 0.557), 0.798 (0.755, 0.836) and 0.988 (0.978, 0.994) and the specificity were 0.994 (0.993, 0.995), 1 (0.999, 1) and 1 (1, 1). Microscopy displayed no significant differences in sensitivity according to the type of sample. The sensitivities of PCR for sputum, induced sputum, bronchial aspirate and BAL were, 0.821 (0.762, 0.871), 0.643 (0.480, 0.784), 0.837 (0.748, 0.904) and 0.759 (0.624, 0.865) respectively and the sensitivity of culture were, 0.993 (0.981, 0.998), 0.980 (0.931, 0.998), 0.965 (0.919, 0.988), and 1 (0.961, 1) respectively. Pairwise comparison of specimens collected from the same patient reported a significantly higher sensitivity of PCR on bronchial aspirate over BAL (p < 0.001) and sputum (p < 0.05) and a significantly higher sensitivity of culture on bronchial aspirate over BAL (p < 0.0001). Conclusions: PCR displayed a higher sensitivity and specificity than microscopy for all respiratory specimens, a rational for a smear-independent PCR-based approach to initiate tuberculosis microbial diagnostic. The diagnosis yield of bronchial aspirate was higher than BAL. Therefore, PCR should be systematically performed also on bronchial aspirates when available.

Overruling of Procalcitonin-Guided Antibiotics for Lower Respiratory Tract Infections in Primary Care: Ancillary Study of a Randomized Controlled Trial.

BACKGROUND: Lower respiratory tract infections (LRTIs) in primary care are a promising target for antibiotic stewardship. A clinical trial in Switzerland showed a large decrease in antibiotic prescriptions with procalcitonin guidance (cut-off < 0.25 µg/L) compared with usual care. However, one-third of patients with low procalcitonin at baseline received antibiotics by day 28. AIM: To explore the factors associated with the overruling of initial procalcitonin guidance. DESIGN AND SETTING: Secondary analysis of a cluster randomized trial in which patients with an LRTI were included. METHOD: Using the characteristics of patients, their disease, and general practitioners (GPs), we conducted a multivariate logistic regression, adjusted for clustering. RESULTS: Ninety-five out of 301 (32%) patients with low procalcitonin received antibiotics by day 28. Factors associated with an overruling of procalcitonin guidance were: a history of chest pain (adjusted OR [aOR] 1.81, 95% confidence interval 1.03-3.17); a prescription of chest X-ray by the GP (aOR 4.65, 2.32-9.34); a C-reactive protein measured retrospectively above 100 mg/L (aOR 7.48, 2.34-23.93, reference ≤ 20 mg/L); the location of the GP practice in an urban setting (aOR 2.27, 1.18-4.37); and the GP's number of years of experience (aOR per year 1.05, 1.01-1.09). CONCLUSIONS: Overruling of procalcitonin guidance was associated with GPs' socio-demographic characteristics, pointing to the general behavioral problem of overprescription by physicians. Continuous medical education and communication training might support the successful implementation of procalcitonin point-of-care tests aimed at antibiotic stewardship.

Antigen rapid tests, nasopharyngeal PCR and saliva PCR to detect SARS-CoV-2: A prospective comparative clinical trial.

BACKGROUND: Nasopharyngeal antigen Rapid Diagnostic Tests (RDTs), saliva RT-PCR and nasopharyngeal (NP) RT-PCR have shown different performance characteristics to detect patients infected by SARS-CoV-2, according to the viral load (VL)-and thus transmissibility. METHODS: In October 2020, we conducted a prospective trial involving patients presenting at testing centres with symptoms of COVID-19. We compared detection rates and performance of RDT, saliva PCR and nasopharyngeal (NP) PCR, according to VL and symptoms duration. RESULTS: Out of 949 patients enrolled, 928 patients had all three tests performed. Detection rates were 35.2% (95%CI 32.2-38.4%) by RDT, 39.8% (36.6-43.0%) by saliva PCR, 40.1% (36.9-43.3%) by NP PCR, and 41.5% (38.3-44.7%) by any test. For those with viral loads (VL) ≥106 copies/ml, detection rates were 30.3% (27.3-33.3), 31.4% (28.4-34.5), 31.5% (28.5-34.6), and 31.6% (28.6-34.7%) respectively. Sensitivity of RDT compared to NP PCR was 87.4% (83.6-90.6%) for all positive patients, 94.5% (91.5-96.7%) for those with VL≥105 and 96.5% (93.6-98.3%) for those with VL≥106. Sensitivity of STANDARD-Q®, Panbio™ and COVID-VIRO® Ag tests were 92.9% (86.4-96.9%), 86.1% (78.6-91.7%) and 84.1% (76.9-89.7%), respectively. For those with VL≥106, sensitivity was 96.6% (90.5-99.3%), 97.8% (92.1-99.7%) and 95.3% (89.4-98.5%) respectively. No patient with VL<104 was detected by RDT. Specificity of RDT was 100% (99.3-100%) compared to any PCR. RDT sensitivity was similar <4 days (87.8%, 83.5-91.3%) and ≥4 days (85.7%, 75.9-92.6%) after symptoms onset (p = 0.6). Sensitivity of saliva and NP PCR were 95.7% (93.1-97.5%) and 96.5% (94.1-98.1%), respectively, compared to the other PCR. CONCLUSIONS: RDT results allow rapid identification of COVID cases with immediate isolation of most contagious individuals. RDT can thus be a game changer both in ambulatory care and community testing aimed at stopping transmission chains, and even more so in resource-constrained settings thanks to its very low price. When PCR is performed, saliva could replace NP swabbing. TRIAL REGISTRATION: ClinicalTrial.gov Identifier: NCT04613310 (03/11/2020).

Comparison of Nasopharyngeal and Saliva Swab Nucleic Acid Amplification and Rapid Antigen Testing To Detect Omicron SARS-CoV-2 Variant of Concern: a Prospective Clinical Trial (OMICRON).

In November 2021, the World Health Organization declared the Omicron variant (B.1.1.519) a variant of concern. Since then, worries have been expressed regarding the ability of usual diagnostic tests to detect the Omicron variant. In addition, some recently published data suggested that the salivary reverse transcription (RT)-PCR might perform better than the current gold standard, nasopharyngeal (NP) RT-PCR. In this study, we aimed to compare the sensitivities of nasopharyngeal and saliva RT-PCR and assess the diagnostic performances of rapid antigen testing (RAT) in nasopharyngeal and saliva samples. We conducted a prospective clinical study among symptomatic health care professionals consulting the occupational health service of our hospital for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening and hospitalized patients in internal medicine/intensive care wards screened for SARS-CoV-2 with COVID-19-compatible symptoms. A composite outcome considering NP PCR and/or saliva PCR was used as a reference standard to define COVID-19 cases. A total of 475 paired NP/saliva specimens have been collected with a positivity rate of 40% (n = 192). NP and salivary RT-PCR exhibited sensitivities of 98% (95% CI, 94 to 99%) and 87% (95% CI, 81 to 91%), respectively, for outpatients (n = 453) and 94% (95% CI, 72 to 99%) and 69% (95% CI, 44 to 86%), respectively, for hospitalized patients (n = 22). Nasopharyngeal rapid antigen testing exhibited much lower diagnostic performances (sensitivity of 66% and 31% for outpatients and inpatients, respectively), while saliva RAT showed a sensitivity of less than 5% in both groups. Nasopharyngeal RT-PCR testing remains the gold standard for SARS-CoV-2 Omicron variant screening. Salivary RT-PCR can be used as an alternative in case of contraindication to perform NP sampling. The use of RAT should be limited to settings where access to molecular diagnostic methods is lacking. IMPORTANCE The Omicron variant of concern spread rapidly since it was first reported in November 2021 and currently accounts for the vast majority of new infections worldwide. Recent reports suggest that saliva sampling might outweigh nasopharyngeal sampling for the diagnosis of the Omicron variant. Nevertheless, data investigating the best diagnostic strategy specifically for the Omicron variant of concern remain scarce. This study fills this gap in current knowledge and elucidates the question of which strategy to use in which patient. It provides a new basis for further improving COVID-19 screening programs and managing patients suspected to have COVID-19.

Antibody response and intra-host viral evolution after plasma therapy in COVID-19 patients pre-exposed or not to B-cell-depleting agents.

Administration of plasma therapy may contribute to viral control and survival of COVID-19 patients receiving B-cell-depleting agents that impair humoral immunity. However, little is known on the impact of anti-CD20 pre-exposition on the kinetics of SARS-CoV-2-specific antibodies. Here, we evaluated the relationship between anti-spike immunoglobulin G (IgG) kinetics and the clinical status or intra-host viral evolution after plasma therapy in 36 eligible hospitalized COVID-19 patients, pre-exposed or not to B-cell-depleting treatments. The majority of anti-CD20 pre-exposed patients (14/17) showed progressive declines of anti-spike IgG titres following plasma therapy, contrasting with the 4/19 patients who had not received B-cell-depleting agents (p = 0.0006). Patients with antibody decay also depicted prolonged clinical symptoms according to the World Health Organization (WHO) severity classification (p = 0.0267) and SARS-CoV-2 viral loads (p = 0.0032) before complete virus clearance. Moreover, they had higher mutation rates than patients able to mount an endogenous humoral response (p = 0.015), including three patients with one to four spike mutations, potentially associated with immune escape. No relevant differences were observed between patients treated with plasma from convalescent and/or mRNA-vaccinated donors. Our study emphasizes the need for an individualized clinical care and follow-up in the management of COVID-19 patients with B-cell lymphopenia.

Assessment of SARS-CoV-2 tests costs and reimbursement tariffs readjustments during the COVID-19 pandemic.

INTRODUCTION: While laboratories have been facing limited supplies of reagents for diagnostic tests throughout the course of the COVID-19 pandemic, national and international health plans, as well as billing costs, have been constantly adjusted in order to optimize the use of resources. We aimed to assess the impact of SARS-CoV-2 test costs and reimbursement tariff adjustments on diagnostic strategies in Switzerland to determine the advantages and disadvantages of different costs and resource saving plans. MATERIALS AND METHODS: We specifically assessed the cost of diagnostic SARS-COV-2 RT-PCR using five different approaches: i) in-house platform, ii) cobas 6800® (Roche, Basel, Switzerland), iii) GeneXpert® SARS-CoV-2 test (Cepheid, Sunnyvale, CA, USA), iv) VIASURE SARS-CoV-2 (N1 + N2) Real-Time PCR Detection Kit for BD MAX™ (Becton Dickinson, Franklin Lake, NJ, USA), v) cobas® Liat® SARS-CoV-2 & Influenza A/B (Roche, Basel, Switzerland). We compared these costs to the evolution of the reimbursement tariffs. RESULTS: The cost of a single RT-PCR test varied greatly (as did the volume of tests performed), ranging from as high as 180 CHF per test at the beginning of the pandemic (February to April 2020) to as low as 82 CHF per test at the end of 2020. Depending on the time period within the pandemic, higher costs did not necessarily mean greater benefits for the laboratories. The costs of molecular reagents for rapid tests were higher than of those for classic RT-PCR platforms, but the rapid tests had reduced turnaround times (TATs), thus improving patient care and enabling more efficient implementation of isolation measures, as well as reducing the burden of possible nosocomial infections. At the same time, there were periods when the production or distribution of these reagents was insufficient, and only the use of several different molecular platforms allowed us to sustain the high number of tests requested. CONCLUSIONS: Cost-saving plans need to be thoroughly assessed and constantly adjusted according to the epidemiological situation, the clinical context and the national resources in order to always guarantee that the highest performing diagnostic solutions are available. Not all cost-saving strategies guarantee good analytical performance.

Utility of Polymerase Chain Reaction in Nasopharyngeal Swabs for Identifying Respiratory Bacteria Causing Community-Acquired Pneumonia.

Timely identification of a pathogen in lower respiratory tract infections (LRTI) can support appropriate antibiotics use. The difficulty of obtaining lower respiratory tract (LRT) samples limits the utility of point-of-care syndromic molecular assays. We assessed the performance of the FilmArray Pneumonia plus panel (FilmArray PP) in nasopharyngeal (NP) swab for detection of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Patients in the study included retrospectively consenting adults who attended the emergency department of Lausanne University Hospital between February 2019 and August 2020 for a community-acquired LRTI, with available NP swab and a high-quality LRT sample. These samples were tested with the FilmArray PP (cutoff of ≥104 copies/mL). Positive (PPA) and negative percent agreement (NPA) of FilmArray PP in NP swab were calculated, using (i) FilmArray PP in LRT sample and (ii) standard microbiological tests as reference standards. To assess the performance of a lower detection cutoff, NP samples were also tested with an in-house PCR (cutoff of ≥10 copies/mL) for S. pneumoniae and H. influenzae. Overall, 118 patients were included. FilmArray PP in LRT sample and standard microbiology tests detected S. pneumoniae in 19/118 and 12/118, H. influenzae in 44/118 and 19/118, and M. catarrhalis in 14/118 and 0/118, respectively. Using LRT FilmArray PP as reference, PPA and NPA of FilmArray PP on NP were 58% and 100% for S. pneumoniae, 61% and 100% for H. influenzae, and 57% and 99% for M. catarrhalis. Using standard diagnostic tests as reference, PPA and NPA were 58% and 96% for S. pneumoniae, 74% and 87% for H. influenzae, and indefinite and 92% for M. catarrhalis. Using a lower cutoff on NP (≥102 copies/mL), PPA was 68% for S. pneumoniae and 77% for H. influenzae with LRT FilmArray PP as reference. FilmArray PP in NP swabs has a limited PPA for identifying the most common etiologies of community-acquired LRTI irrespective of the reference standard, preventing its use for withholding antibiotics. The PCR detection cutoff does not explain the low PPA. The excellent NPA suggests the use of NP PCR results for rapidly targeted antimicrobial therapy. IMPORTANCE Timely identification of a pathogen in patients with lower respiratory tract infections is of paramount importance to avoid inappropriate antibiotic prescription. We aimed to evaluate the performance of a rapid syndromic molecular assay in nasopharyngeal swabs for identifying the most common bacterial causes of lower respiratory tract infections in adults (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis). Our data show that nasopharyngeal molecular assay has a good concordance with lower respiratory tract sample when positive but not when negative. A positive result is therefore concordant with a lower respiratory tract infection and can be used to target antibiotics. Nevertheless, a negative result does not have a good concordance, so it cannot be used to withhold antibiotics. Our findings illustrate the potential utility of these easily collected samples for the management of patients with lower respiratory tract infections.

[Pulmonary tularemia : a diagnosis not to be missed]. / Tularémie pulmonaire : un diagnostic à ne pas manquer.

Tularemia (caused by the facultative intracellular Gram-negative bacillus Francisella tularensis) is an endemic zoonotic disease in Europe, which exhibits different clinical patterns. Following the glandular form, pneumonia is the second most frequent manifestation in Switzerland. Pulmonary tularemia often has a subacute course and fails to respond to beta-lactam antibiotics. It can also mimic tuberculosis, because of the presence of systemic symptoms, such as fever, sweats and weight loss. History of animal exposure is not always reported. Clinicians should be aware of pulmonary tularemia. They should be able to diagnose it with appropriate tools (PCR, serology) and initiate appropriate therapy (fluoroquinolones, tetracyclines or aminoglycosides).

La tularémie (causée par le bacille Gram négatif intracellulaire facultatif Francisella tularensis) est une zoonose endémique en Europe qui peut se présenter sous divers syndromes cliniques. Après la forme glandulaire, la pneumonie est la deuxième manifestation la plus courante en Suisse. La tularémie pulmonaire se caractérise par une évolution souvent subaiguë qui ne répond pas aux antibiotiques de type bêtalactamines. Elle peut aussi être confondue avec une tuberculose en raison des symptômes systémiques associés (fièvre, sudations, perte pondérale). L'exposition animale n'est pas toujours documentée. Il est important pour le clinicien de savoir reconnaître cette forme de pneumonie atypique, la diagnostiquer à l'aide des bons outils (PCR ou sérologie) et la traiter de manière appropriée (fluoroquinolones, tétracyclines ou aminoglycosides).

Post­COVID­19 Syndrome in Outpatients: a Cohort Study.

BACKGROUND: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. OBJECTIVES: To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. PARTICIPANTS: Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). DESIGN: Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics. MAIN MEASURES: Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. KEY RESULTS: The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms. CONCLUSIONS: More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.

A refractory tenosynovitis of the wrist: a case report.

BACKGROUND: Mycobacterium malmoense is a species of slow-growing nontuberculous mycobacteria. It causes mostly pulmonary infections or lymphadenitis in children, but is increasingly encountered in isolated tenosynovitis in adults. Diagnosis is often delayed because of the rarity of the condition and the difficulty of culturing the bacteria. CASE PRESENTATION: We report on a rare association of seronegative polyarthritis with infectious nontuberculous mycobacteria tenosynovitis. A 65-year-old Caucasian female was referred to our clinic because of persisting tenosynovitis of the finger flexor tendons of her right hand, despite two previous synovectomies. She also reported bilateral shoulder and left wrist pain. Paraclinical investigations showed slightly elevated inflammatory parameters. Ultrasound showed synovitis of metacarpophalangeal joints of the right hand and right knee, and a bilateral subacromial bursitis. Hand magnetic resonance imaging also revealed an erosive carpal synovitis. Bacteriological analysis of the second tenosynovectomy specimen showed no growths in aerobic and anaerobic cultures. An additional synovial fluid analysis of the wrist joint was negative for mycobacteria and crystals. Seronegative polyarthritis was suspected, but the initiated immunosuppressive treatment with prednisolone and methotrexate resulted in no clinical improvement of the tenosynovitis. Yet the other joints responded well, and the inflammatory parameters normalized. The immunosuppression was later stopped because of side effects. Due to massive worsening of the tenosynovitis, a third synovectomy was performed. Mycobacterium malmoense was identified on biopsy, leading to the diagnosis of infectious tenosynovitis. At this point, we started an antituberculous therapy, with incomplete response. A combination of antimicrobial and immunosuppressive treatment finally led to the desired clinical improvement. CONCLUSION: The treatment of nontuberculous mycobacteria tenosynovitis is not well established, but combining antibiotics with surgical debridement is probably the most adequate approach. Our case highlights the importance of having a high clinical suspicion of an atypical infection in patients with inflammatory tenosynovitis not responding to usual care.

External Quality Assessment of SARS-CoV-2 Sequencing: an ESGMD-SSM Pilot Trial across 15 European Laboratories.

This first pilot trial on external quality assessment (EQA) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) whole-genome sequencing, initiated by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Genomic and Molecular Diagnostics (ESGMD) and the Swiss Society for Microbiology (SSM), aims to build a framework between laboratories in order to improve pathogen surveillance sequencing. Ten samples with various viral loads were sent out to 15 clinical laboratories that had free choice of sequencing methods and bioinformatic analyses. The key aspects on which the individual centers were compared were the identification of (i) single nucleotide polymorphisms (SNPs) and indels, (ii) Pango lineages, and (iii) clusters between samples. The participating laboratories used a wide array of methods and analysis pipelines. Most were able to generate whole genomes for all samples. Genomes were sequenced to various depths (up to a 100-fold difference across centers). There was a very good consensus regarding the majority of reporting criteria, but there were a few discrepancies in lineage and cluster assignments. Additionally, there were inconsistencies in variant calling. The main reasons for discrepancies were missing data, bioinformatic choices, and interpretation of data. The pilot EQA was overall a success. It was able to show the high quality of participating laboratories and provide valuable feedback in cases where problems occurred, thereby improving the sequencing setup of laboratories. A larger follow-up EQA should, however, improve on defining the variables and format of the report. Additionally, contamination and/or minority variants should be a further aspect of assessment.