CRP under 130 mg/L rules out the diagnosis of Legionella pneumophila serogroup 1 (URINELLA Study).

INTRODUCTION: In case of pneumonia, some biological findings are suggestive for Legionnaire's disease (LD) including C-reactive protein (CRP). A low level of CRP is predictive for negative Legionella Urinary-Antigen-Test (L-UAT). METHOD: Observational retrospective study in Nord-Franche-Comté Hospital with external validation in Besançon University Hospital, France which included all adults with L-UAT performed during January 2018 to December 2022. The objective was to determine CRP optimal threshold to predict a L-UAT negative result. RESULTS: URINELLA included 5051 patients (83 with positive L-UAT). CRP optimal threshold was 131.9 mg/L, with a negative predictive value (NPV) at 100%, sensitivity at 100% and specificity at 58.0%. The AUC of the ROC-Curve was at 88.7% (95% CI, 86.3-91.1). External validation in Besançon Hospital patients showed an AUC at 89.8% (95% CI, 85.5-94.1) and NPV, sensitivity and specificity was respectively 99.9%, 97.6% and 59.1% for a CRP threshold at 131.9 mg/L; after exclusion of immunosuppressed patients, index sensitivity and NPV reached also 100%. CONCLUSION: In case of pneumonia suspicion with a CRP level under 130 mg/L (independently of the severity) L-UAT is useless in immunocompetent patients with a NPV at 100%. We must remain cautious in patients with symptoms onset less than 48 h before CRP dosage.

Campylobacter fetus Invasive Infections and Risks for Death, France, 2000-2021.

Campylobacter fetus accounts for 1% of Campylobacter spp. infections, but prevalence of bacteremia and risk for death are high. To determine clinical features of C. fetus infections and risks for death, we conducted a retrospective observational study of all adult inpatients with a confirmed C. fetus infection in Nord Franche-Comté Hospital, Trevenans, France, during January 2000-December 2021. Among 991 patients with isolated Campylobacter spp. strains, we identified 39 (4%) with culture-positive C. fetus infections, of which 33 had complete records and underwent further analysis; 21 had documented bacteremia and 12 did not. Secondary localizations were reported for 7 (33%) patients with C. fetus bacteremia, of which 5 exhibited a predilection for vascular infections (including 3 with mycotic aneurysm). Another 7 (33%) patients with C. fetus bacteremia died within 30 days. Significant risk factors associated with death within 30 days were dyspnea, quick sequential organ failure assessment score >2 at admission, and septic shock.

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.

Biomarker variation in patients successfully treated with tocilizumab for severe coronavirus disease 2019 (COVID-19): results of a multidisciplinary collaboration.

OBJECTIVES: Acute respiratory distress syndrome (ARDS) related to SARS-CoV-2 is likely due to a cytokine storm characterised by a major release of pro-inflammatory cytokines, including interleukin-6 (IL-6). Blocking excessive IL-6 production might be the key to the COVID-19-ARDS treatment. Beneficial effects of IL-6 blockade using a humanised anti-IL-6 receptor antibody, tocilizumab (TCZ) were previously reported in patients with COVID-19 related ARDS. The aim of the study was to study the variation over time of several biomarkers, demonstrated to be predictors of poor prognostic, in subjects successfully treated with TCZ for severe COVID-19. METHODS: Retrospective analysis of a case series of patients with COVID-19-ARDS, evidenced by RT-PCR and lung CT-scan. Patients with increasing O2 requirements, within the window of opportunity for TCZ treatment (Day 7 to Day 17 after onset of symptoms) were treated with TCZ (2 infusions of 8 mg/kg). Demographic, biological and clinical data were collected from the patients' files. Serum levels of CRP, ferritin, fibrinogen, lymphocytes, platelets, creatinine, D-dimer and liver enzymes were assayed at the time of the first TCZ administration, then every two days for 8 days. RESULTS: 40 patients were treated with TCZ. Most of them had several comorbidities, and all had multiple biological abnormalities (lymphopenia, increased CRP, ferritin, fibrinogen, D-dimer, liver enzymes). 30 patients (75%) benefited from TCZ and 10 patients died. In the survivors, following TCZ administration CRP decreased dramatically as early as day 4 (-86.7%, p<0.0001) and returned to normal at day 6. Fibrinogen and lymphocyte count returned to normal values at day 6. Ferritin also decreased significantly. No significant change was observed for D-dimer (p=0.68) and other studied biomarkers (haemoglobin, leucocyte count, AST). CONCLUSIONS: In patients with COVID-19 acute respiratory distress syndrome, treatment with TCZ resulted in favourable evolution in 75% of the cases. Biomarkers of inflammation (CRP, ferritin, fibrinogen) decreased dramatically as early as the 4th day after TCZ injection. Lymphopenia, a predictor of poor prognostic, was reversed 6 days after TCZ injection.

Prolonged SARS-CoV-2 Infection in Patients Receiving Anti-CD20 Monoclonal Antibodies: A Diagnostic Challenged by Negative Nasopharyngeal RT-PCR and Successful Treatment with COVID-19 High-Titer Convalescent Plasma.

We highlighted in this current paper similar prolonged respiratory presentation with COVID-19 pneumonia in four severely immunocompromised patients currently being treated with anti-CD20 monoclonal antibodies (mAbs), such as ocrelizumab and rituximab, for multiple sclerosis or rheumatoid polyarthritis. Real-time reverse transcription-polymerase chain reaction on a nasopharyngeal swab specimen was negative in all patients. SARS-CoV-2 infection was confirmed from bronchoalveolar lavage fluid. A high titer of post-vaccine COVID-19 convalescent plasma was administered with complete recovery in all patients.

Asthma and Cacosmia Could Be Predictive Factors of Olfactory Dysfunction Persistence 9 Months after SARS-CoV-2 Infection: The ANOSVID Study.

Background. Long-term evolution data of olfactory disorders (OD) in COVID-19 are limited. Method. ANOSVID is a retrospective study in Nord Franche-Comté Hospital (France) that included COVID-19 patients from the first wave. The aim was to describe OD evolution, especially in patients with persistent OD (p-OD group) in comparison with patients with resolved OD (r-OD group). Results. Among 354 COVID-19 patients, 229 reported OD were included. Eighty-five percent of patients (n = 195) recovered from their OD within 90 days. However, 9.5 months (in average) after symptoms onset, OD were persisting in 93 patients (40.6%) and resolved in 136 patients (59.4%). In the p-OD group (n = 93), the mean age was 51.4 years (19-98) ± 20.2, and 65 patients (69.9%) were female; the three main comorbidities in the p-OD group were: asthma (20.4%, n = 19), allergic rhinitis (19.4%, n = 18), and arterial hypertension (16.1%, n = 15). Eleven patients (12%) presented anosmia, and 82 patients (88%) presented hyposmia. Asthma was more described in p-OD group than r-OD group (19 (20.4%) versus 10 (7.4%), p = 0.006). Cacosmia was more described in p-OD group than r-OD group (27 (29.0%) versus 18 (13.2%), p = 0.005). There was no significant difference between the two groups concerning other comorbidities and symptoms, clinical, biological, and imaging findings, and outcome or about the impact of OD on the quality of life of the patients between the p-OD group and r-OD group. sQOD-NS brief version score was 10.7 ± 5.89 and 12.0 ± 6.03, respectively (p = 0.137). Conclusion. Forty-one percent of patients with OD reported OD persistence 9.5 months after COVID-19 (hyposmia in 88% of cases). Asthma and cacosmia could be predictive factors of OD persistence.

Shigella sonnei, an emerging multidrug-resistant sexually transmitted pathogen in Franche-Comté, France.

Shigella sonnei (S. sonnei) is sometimes sexually transmitted. Men, who have sex with men (MSM), may have sexual behaviours different from heterosexual population, and thus may be at risk for S. sonnei infection. We describe three cases of multidrug-resistant S. sonnei in MSM (one HIV-infected patient and two patients receiving pre-exposure prophylaxis against HIV). S. sonnei was isolated from stool specimens and all patients were successfully treated with parenteral third-generation cephalosporins following laboratory confirmation that the isolates were resistant to azithromycin. Two men (patients 2 and 3) were linked epidemiologically. These cases highlight the emergence of this pathogen and its association with some sexual behaviours among MSM in Franche-Comté, France.

Recurrence of COVID-19 after recovery ? A case series in health care workers, France.

We describe 3 cases of coronavirus disease 2019 in health care workers in France involving presumed clinical and microbiological recurrence after recovery. All patients were immunocompetent with clinical mild form. These cases highlight the possibility of coronavirus disease-recurrence.

Angioedema and COVID-19: A New Dermatological Manifestation?

The main localization of SARS-CoV-2 infection is the respiratory tract. Digestive and otorhinolaryngological localizations are also reported. More recently, dermatological manifestations have been reported during Coronavirus disease-19 (COVID-19). We report a case of a labial angioedema in a patient with confirmed COVID-19.

COVEVOL: Natural Evolution at 6 Months of COVID-19.

Many studies have investigated post-COVID symptoms, but the predictors of symptom persistence remain unknown. The objective was to describe the natural course of the disease at 6 months and to identify possible factors favoring the resurgence or persistence of these symptoms. COVEVOL is a retrospective observational descriptive study of 74 patients. All patients with positive SARS-CoV-2 PCR from March 2020 were included. We compared a group with symptom persistence (PS group) with another group without symptom persistence (no-PS group). Fifty-three out of seventy-four patients (71.62%) described at least one persistent symptom at 6 months of SARS-CoV-2 infection. In the PS group, 56.6% were women and the average age was 54.7 years old [21-89.2] ± 16.9. The main symptoms were asthenia (56.6%, n = 30), dyspnea (34%, n = 18), anxiety (32.1% n = 17), anosmia (24.5%, n = 13) and agueusia (15.1% n = 8). Ten patients (13.51%) presented a resurgence in symptoms. Patients in the PS group were older (p = 0.0048), had a higher BMI (p = 0.0071), and were more frequently hospitalized (p = 0.0359) compared to the no-PS group. Odynophagia and nasal obstruction were less present in the inaugural symptoms of COVID-19 in the PS group (p = 0.0202 and p = 0.0332). Persistent post-COVID syndromes are common and identification of contributing factors is necessary for understanding this phenomenon and appropriate management.

Leclercia adecarboxylata as Emerging Pathogen in Human Infections: Clinical Features and Antimicrobial Susceptibility Testing.

(1) Background: Leclercia adecarboxylata (L. adecarboxylata) is a gram-negative bacillus of the Enterobacteriaceae family, which is uncommonly isolated from clinical specimens. L. adecarboxylata is considered as an aquatic opportunistic pathogen and most of the human infections are polymicrobial and usually occur in immunocompromised hosts. (2) Methods: In this retrospective study, we included all L. adecarboxylata strains since the introduction of MALDI-TOF MS in the Microbiology Department of Nord Franche-Comté Hospital, France (from 1 March 2015 to 31 July 2019). We studied demographic characteristics, comorbidities, characteristics of the current infection and outcome as well as antimicrobial susceptibility testing in all isolates. (3) Results: A total of 8 samples were identified (in 6 patients (4M/2F), with a recurrent L. adecarboxylata infection in 2 patients). The patients' mean age was 66.2 years (range: 19-84). All patients were considered as immunocompetent, except a peritoneal dialysis patient with kidney transplantation. An exposition to an aquatic environment was identified in one patient. The most prevalent clinical feature was catheter-associated male urinary tract infection (in 3 cases) followed by ventilator-associated pneumonia (in 2 cases). One of 6 patients presented L. adecarboxylata bacteremia. L. adecarboxylata was part of a polymicrobial infection in 4 patients. The isolates showed a high susceptibility to all tested antibiotics, except one strain, which was resistant to fosfomycin. All patients with L. adecarboxylata infection were treated with antibiotics with a favorable outcome. (4) Conclusion: This study confirms the pathogenicity of L. adecarboxylata, even in immunocompetent patients, with a high susceptibility to antibiotics.

Systematic Review and Subgroup Meta-analysis of Randomized Trials to Determine Tocilizumab's Place in COVID-19 Pneumonia.

INTRODUCTION: Tocilizumab randomized clinical trial results are heterogeneous because of the heterogenous population included in them. METHODS: We conducted a meta-analysis with subgroup meta-analysis (PRISMA guidelines) between severe and non-severe COVID-19. RESULTS: We included nine trials. Overall, the mortality rate was 24.5% (821/3357) in the tocilizumab group and 29.1% (908/3125) in the control group at day 28-30 (pooled OR, 0.85; 95% CI 0.76-0.96; p = 0.006). Considering the subgroup analysis, this benefit on mortality was confirmed and amplified in the severe COVID-19 group (pooled OR, 0.82; 95% CI 0.73-0.93; p = 0.001) but not in the non-severe COVID-19 group (pooled OR, 1.46; 95% CI 0.91-2.34; p = 0.12). For patients who were not mechanically ventilated at baseline (5523/6482), the pooled OR (0.74; 95% CI 0.64-0.85; p < 0.0001) for mechanical ventilation incidence at day 28-30 was in favor of tocilizumab (cumulative incidence of 14.8% versus 19.4% in tocilizumab and control arm, respectively). This benefit was confirmed in both subgroups, i.e., severe and non-severe COVID-19. CONCLUSION: Tocilizumab is an effective treatment in hospitalized patients with COVID-19 and hypoxemia by improving survival and decreasing mechanical ventilation requirement. The greatest benefit is observed in severe COVID-19.

Post-COVID-19 Syndrome: Nine Months after SARS-CoV-2 Infection in a Cohort of 354 Patients: Data from the First Wave of COVID-19 in Nord Franche-Comté Hospital, France.

(1) Background. Post-COVID-19 syndrome is defined as the persistence of symptoms after confirmed SARS-CoV-2 infection. (2) Methods. ANOSVID is an observational retrospective study in Nord Franche-Comté Hospital in France that included adult COVID-19 patients confirmed by RT-PCR from 1 March 2020 to 31 May 2020. The aim was to describe patients with post-COVID-19 syndrome with persistent symptoms (PS group) and to compare them with the patients without persistent symptoms (no-PS group). (3) Results. Of the 354 COVID-19 patients, 35.9% (n = 127) reported persistence of at least one symptom after a mean of 289.1 ± 24.5 days after symptom onset. Moreover, 115 patients reported a recurrence of symptoms after recovery, and only 12 patients reported continuous symptoms. The mean age of patients was 48.6 years (19-93) ± 19.4, and 81 patients (63.8%) were female. Patients in the PS group had a longer duration of symptoms of initial acute SARS-CoV-2 infection than patients in the no-PS group (respectively, 57.1 ± 82.1 days versus 29.7 ± 42.1 days, p < 0.001). A majority of patients (n = 104, 81.9%) reported three or more symptoms. The most prevalent persistent symptoms were loss of smell (74.0%, n = 94), fatigue (53.5%, n = 68), loss of taste (31.5%, n = 40), and dyspnea (30.7%, n = 39). These were followed by pain symptoms (26.8% (n = 34), 26.0% (n = 33), 24.4% (n = 31); headache, arthralgia, and myalgia, respectively). More than half of patients reporting persistent symptoms (58%, n = 73) were healthcare workers (HCWs). Among outpatients, this population was more present in the PS group than the no-PS group ((86.6%) n = 71/82 versus (72.2%) n = 109/151, p = 0.012). Post-COVID-19 syndrome was more frequent in patients with a past history of chronic rhinosinusitis (8.7% (n = 11%) versus 1.3% (n = 3), p < 0.001). No significant difference was found regarding clinical characteristics and outcome, laboratory, imaging findings, and treatment received in the two groups. (4) Conclusions. More than a third of our COVID-19 patients presented persistent symptoms after SARS-CoV-2 infection, particularly through loss of smell, loss of taste, fatigue, and dyspnea, with a high prevalence in HCWs among COVID-19 outpatients.

New loss of smell and taste: Uncommon symptoms in COVID-19 patients on Nord Franche-Comte cluster, France.

BACKGROUND: New loss of smell or taste was not included as common symptoms of COVID-19 until March 2020 when the pandemic started in Western countries. We want to describe the prevalence and features of anosmia and dysgeusia in COVID-19 patients. METHODS: We retrospectively investigated the clinical features of confirmed cases of COVID-19 in Nord Franche-Comté Hospital, Trevenans, France, between March, 1st and March, 14th 2020. We used SARS-CoV-2 real time RT-PCR in respiratory samples to confirm the cases. RESULTS: Of 70 patient enrolled, the mean age was 57.0 years and 29 patients (41%) were men. Median Charlson comorbidity index was 1.70(±2.5). Twenty-seven (39%) patients had pneumonia. Fatigue (93% [65]), cough (80% [55]) and fever (77% [54]) were the three main symptoms. Neurologic symptoms were present in more than half of the patients: anosmia (53% [37]) and dysgeusia (48% [34]). The mean duration of anosmia was 7.4 (±5, [1-21]) days, 51% (36/70) recovered before 28 days of evolution. Only one patient with anosmia had not recovered at the end of the follow-up. Patients with anosmia had less often a pneumonia (10/37 vs 17/33, p = 0.036), were less often hospitalized (13/37 vs 20/33, p = 0.033) and needed less often oxygen therapy (6/37 vs 17/33, p = 0.002) than patients without anosmia. There were no statistically differences for viral load between patients with anosmia and patients without anosmia (5.5 [2.0-8.6] vs 5.3 [2.1-8.5] log copies/ml respectively, p = 0.670). The fatality of COVID-19 in our study was 6% with four deaths. CONCLUSIONS: Anosmia and dysgeusia are present in half of COVID-19 patients. The mean duration of anosmia was 7 days and the outcome seems favorable in less than 28 days.

COVID-19: comparative clinical features and outcome in 114 patients with or without pneumonia (Nord Franche-Comte Hospital, France).

COVID-19 patients (n = 114) were included (55 patients with pneumonia (group P) and 59 without pneumonia (group NP). Patients in group P were older (69 (±17) years vs 46 (±16); p < 0.001) with a male predominance (58.2% vs 27.1%; p < 0.001). The symptoms which were statistically more frequents in patients with pneumonia were fever ≥ 38 °C (93% vs 70%; p = 0.002) and dyspnea (73% vs 22%; p < 0.001). Symptoms such as facial headache (42% vs 15%; p = 0.001), sore throat (39% vs 16%; p = 0.007), dysgeusia (61% vs 33%; p = 0.003), anosmia (63% vs 31%; p = 0.001) were statistically more frequents in patients without pneumonia.

Diarrhea: An underestimated symptom in Coronavirus disease 2019.

In a retrospective study in the Nord Franche-Comté hospital conducted between March 1st and March 17th 2020, and compared to the review of Li et al., diarrhea was a main symptom in patients with COVID-19. Out of the 114 patients, 55 (48%) had diarrhea; it was the fifth most common symptom. In the group of patients with diarrhea, the median age was 56 years (±18) and 32 (58%) were female. Only 2 patients (3.6%) had a past history of inflammatory bowel disease. Fifty-six percent of patients (n=30/54) were hospitalised. Diarrhea appeared 4.5 days (±1.8) after the onset of the first other symptoms in COVID-19. Of the 55 patients with diarrhea, 29 (52.7%) had at least one simultaneous gastrointestinal (GI) symptom other than diarrhea. Twenty-five patients (45.5%) had nausea, 19 patients (34.5%) had abdominal pain and 9 (16.3%) had vomiting. Myalgia, sore throat, sneezing and the other GI symptoms were statistically more frequent in the group with diarrhea than in the group without diarrhea (P<0.05).