Structural impact of a new spike Y170W mutation detected in early emerging SARS-CoV-2 Omicron variants in France.

To assess the genetic characteristics of the early emerging SARS-CoV-2 Omicron variant strains, we retrospectively analyzed a collection of 150 nasopharyngeal samples taken from a series of outpatient cases tested positive by a referenced qRT-PCR assay during the reported period of Omicron variant emergence in December 2021, in northeastern region of France. Next Generation Sequencing (NGS) analysis of SARS-CoV-2 spike sequences revealed that only 3 (2 %) of these detected strains were Omicron variants, while 147 (98 %) were identified as previously described delta variants. Our phylogenetic analyzes of SARS-CoV-2 RNA genomes showed that these French early emerging Omicron variants may have originated from South Africa or India. In addition, whole viral genome sequences NGS comparison analyzes allowed us to identify an original and uncharacterized Y170W spike mutation that was weakly and transiently detected during the period of SARS-CoV-2 Omicron variant emergence in human populations. Molecular modeling and docking experiments indicated that this original mutated residue Y170W was neither directly involved in binding to the SARS-CoV-2 receptor ACE2 nor in interacting with known neutralizing antibody sites. However, this new mutation may be responsible for preventing the transition from the closed to the open Spike conformation, thus promoting the early emergence of the Omicron variant. Overall, these results underscore the epidemiological utility of a routine whole-genome viral NGS strategy that enables genotypic characterization of emerging or mutant SARS-CoV-2 variants, which could have significant implications for public health policy.

Impact of COVID-19 Pandemic on the Clinical Follow-Up of Patients Living with HIV in Chad: A Retrospective Monocentric Investigation.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on the clinical follow-up of people living with HIV (PLWH) remains poorly documented in Sahelian Africa. We conducted a monocentric retrospective investigation of the outcomes (loss to follow-up [LTFU], transferred, or dead) among a cohort of PLWH receiving antiretroviral treatment (ART) in N'djamena, Chad (December 2019-December 2022). The incidence of LTFU was found to be higher in 2020 than in 2022 (P > 10-4), with increases of incidence of LTFU in the first trimester of 2020 before identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection cases in Chad. The all-cause mortality was low and did not appear to be influenced by SARS-CoV-2 infection waves. Our data reveal a concerning trend of significantly increased LTFU among PLWH receiving ART during the COVID-19 pandemic. Our findings indicate that it is crucial to provide accurate information to ensure the continuity of care for PLWH during a sanitary crisis in Sahelian Africa.

Systemic vasculitis diagnosed during the post-partum period: case report and review of the literature.

INTRODUCTION: The vasculitis diagnosed specifically in the post-partum period are less well known. We report here such a case followed by a descriptive review of the literature. CASE REPORT: A 25 year-old French nurse reported abrupt-onset musculoskeletal pain 15 days after delivery of her first infant. Her first pregnancy was uneventful. The physical examination yielded only bilateral conjunctivitis and purpuric eruption of lower limbs, and complementary investigations evidenced pulmonary renal syndrome in connection with the diagnosis of Granulomatosis with Polyangiitis. METHODS: We screened previous articles in Medline database using keywords (i) "post-partum" or "puerperium" (ii)"peripartum" (iii) "pregnancy" associated with "vasculitis". Full texts were obtained from case reports or cases series whose title or abstract included keywords of interest (or synonyms). These references were secondarily excluded if the diagnosis of vasculitis was not confirmed or made before or more than 6 months after delivery and if vasculitis occurred only in the new born or affected only the cerebral vasculature or the retina. RESULTS: Fifty-six cases of vasculitis diagnosed in the post-partum period were included, 50 (89.3%) were secondary to an immunological process and 44 corresponded to primary vasculitis, 4 were secondary to Systemic Lupus Erythematosus, 1 to cryoglobulinaemia and 1 to cryoglobulinaemia associated with inflammatory bowel disease. The main primary vasculitis diagnosed were Takayasu Arteritis (n = 10), Eosinophilic granulomatosis with polyangiitis (n = 9), Granulomatosis with Polyangiitis (n = 7), Periarteritis Nodosa (n = 5) and Behcet's disease (n = 4). The first symptom occurred before delivery in 26 (59.1%) and maternal death occurred in 4 (9.1%) out of the 44 primary vasculitis cases. CONCLUSION: The vasculitis diagnosed in the post-partum period were mainly primary vasculitis among patients in whom the diagnosis had not been made during pregnancy. In less than half of cases and as described in ours, there were no reported symptoms before delivery. Therefore, the physicians should pay attention to symptoms and keep a high degree of suspicion for vasculitis before as well as after delivery.

Malaria diagnosis in an emergency department before and after the COVID-19 pandemic: a retrospective study.

BACKGROUND: The COVID-19 pandemic impacted access to health facilities. METHODS: We assessed the number of blood smears sampled in the emergency department (ED) among all blood smears performed for malaria in Reims University Hospital before and after 2020. RESULTS: We showed a decrease in the number of blood smears performed after the onset of the COVID-19 pandemic, but only in 2020. The seasonal increase of cases during summer was preserved. All blood smears positive for malaria in 2020 were sampled in the ED. CONCLUSIONS: The ED played a key role in the diagnosis of malaria with the onset of the COVID-19 pandemic.

Early plasma interferon-ß levels as a predictive marker of COVID-19 severe clinical events in adult patients.

We assessed relationships between early peripheral blood type I interferons (IFN) levels, clinical new early warning scores (NEWS), and clinical outcomes in hospitalized coronavirus disease-19 (COVID-19) adult patients. Early IFN-ß levels were lower among patients who further required intensive care unit (ICU) admission than those measured in patients who did not require an ICU admission during severe acute respiratory syndrome coronavirus type 2 infection. IFN-ß levels were inversely correlated with NEWS only in the subgroup of patients who further required ICU admission. To assess whether peripheral blood IFN-ß levels could be a potential relevant biomarker to predict further need for ICU admission, we performed receiver operating characteristic (ROC) curve analyses that showed for all study patients an area under ROC curve of 0.77 growing to 0.86 (p = 0.003) when the analysis was restricted to a subset of patients with NEWS ≥5 at the time of hospital admission. Overall, our findings indicated that early peripheral blood IFN-ß levels might be a relevant predictive marker of further need for an ICU admission in hospitalized COVID-19 adult patients, specifically when clinical score (NEWS) was graded as upper than 5 at the time of hospital admission.

Persistently elevated alkaline phosphatase could be related to Paget's disease of bone in a patient receiving tenofovir disoproxil fumarate.

The prevalence of Paget's disease of bone (PDB) reaches 1-2% of all adults aged ≥55 years old. However, reports describing PDB among HIV positive patients are extremely rare. We report here the case of a HIV positive person receiving tenofovir disoproxil fumarate (DF)-based antiretroviral therapy and who had persistently elevated alkaline phosphatase (AP) revealing PDB. It is well established that tenofovir-DF use is associated with reversible increases in serum AP levels. Clinicians should bear in mind that persistently elevated AP in a person receiving tenofovir DF-based cART could be related to PDB, in particular in person older than 50 years with no other notable biological abnormalities related to kidney tubular dysfunction.

Fusidic acid in a tertiary hospital: an observational study focusing on prescriptions, tolerance and susceptibility of Staphylococcus and Cutibacterium spp. strains from bone samples.

Adverse drug reactions of broad-spectrum fluoroquinolones or rifampicin are not uncommon during osteomyelitis and orthopaedic implant infections (OOII). Thus, we made an overview (i) of the prescription of fusidic acid (FA) and (ii) of FA susceptibility of Staphylococcus sp. and Cutibacterium sp. strains isolated from bone samples. All prescriptions of FA and all bone samples with positive culture for Staphylococcus sp. or Cutibacterium sp. (Reims University Hospital June 2017-May 2021) were included. All Staphylococcus aureus strains were considered as significant, whereas Coagulase-negative Staphylococcus and Cutibacterium spp. strains were not if these strains grew only on one sole sample. The antibiotic susceptibility of Staphylococcus sp. strains and the susceptibility to FA of Cutibacterium sp. strains had been determined using disk diffusion methods, as described for Staphylococcus sp. in the CASFM/EUCAST guidelines. The mean FA consumption was 0.6 daily defined doses/1000 patient days. FA was prescribed for OOII due to Staphylococcus sp. and Cutibacterium sp. in 24 and 2 cases, respectively. Among 401 Staphylococcus sp. strains, there were 254 S. aureus (63.3%), 84 methicillin-resistant (20.9%) and 333 FA-susceptible (83.0%) strains. S. aureus and methicillin-sensitive strains were more likely to be susceptible to FA (p < 0.001). Among 39 Cutibacterium sp. strains, the FA inhibition zone diameter geometric mean was 28.6 mm (24-35 mm), suggesting that all these strains could be considered as susceptible to FA. These data suggested that FA could be more frequently used in OOII due to Staphylococcus sp. and Cutibacterium sp., subject to the absence of other resistant bacteria.

Early Administration of Anti-SARS-CoV-2 Monoclonal Antibodies Prevents Severe COVID-19 in Kidney Transplant Patients.

Introduction: Kidney transplant recipients (KTRs) are prone to develop severe COVID-19 and are less well protected by vaccine than immunocompetent subjects. Thus, the use of neutralizing anti-SARS-CoV-2 monoclonal antibody (MoAb) to confer a passive immunity appears attractive in KTRs. Methods: We performed a French nationwide study to compare COVID-19-related hospitalization, 30-day admission to intensive care unit (ICU), and 30-day death between KTRs who received an early infusion of MoAb (MoAb group) and KTRs who did not (control group). Controls were identified from the COVID-SFT registry (NCT04360707) using a propensity score matching with the following covariates: age, sex, delay between transplantation and infection, induction and maintenance immunosuppressive therapy, initial symptoms, and comorbidities. Results: A total of 80 KTRs received MoAb between February 2021 and June 2021. They were matched to 155 controls. COVID-19-related hospitalization, 30-day admission to ICU, and 30-day death were less frequently observed in the MoAb group (35.0% vs. 49.7%, P = 0.032; 2.5% vs. 15.5%, P = 0.002; 1.25% vs. 11.6%, P = 0.005, respectively). No patient required mechanical ventilation in the MoAb group. The number of patients to treat to prevent 1 death was 9.7. Conclusion: The early use of MoAb in KTRs with a mild form of COVID-19 largely improved outcomes in KTRs.

Surfaces and Air Contamination by Severe Acute Respiratory Syndrome Coronavirus 2 Using High-Flow Nasal Oxygenation or Assisted Mechanical Ventilation in Intensive Care Unit Rooms of Patients With Coronavirus Disease 2019.

BACKGROUND: Understanding patterns of environmental contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for infection prevention policies. METHODS: We screened surfaces and air samples from single-bed intensive-care unit rooms of adult patients with coronavirus disease 2019 (COVID-19) for SARS-CoV-2 RNA and viable viruses. RESULTS: We evidenced viral RNA environmental contamination in 76% of 100 surfaces samples and in 30% of 40 air samples without any viable virus detection by cell culture assays. No significant differences of viral RNA levels on surfaces and in ambient air were observed between rooms of patients with assisted mechanical ventilation and those of patients with a high-flow nasal cannula system. Using an original experimental SARS-CoV-2 infection model of surfaces, we determined that infectious viruses may have been present on benches within 15 hours before the time of sampling in patient rooms. CONCLUSIONS: We observed that SARS-CoV-2 environmental contamination around patients with COVID-19 hospitalized in single-bed ICU rooms was extensive and that a high-flow nasal cannula system did not generate more viral aerosolization than a mechanical ventilation system in patients with COVID-19. Despite an absence of SARS-CoV-2 viable particles in study samples, our experimental model confirmed the need to apply strict environmental disinfection procedures and classic standard and droplet precautions in ICU wards.

Eosinophilia during Hantavirus infection: a cohort study.

BACKGROUND: There are emerging eosinophil-related considerations concerning viral infections. The role of eosinophils has poorly been evaluated during Hantavirus infection. METHODS: The aim of this study was to determine the prevalence of eosinophilia (defined as an eosinophil count above 500 cells/mm3) during haemorrhagic fever with renal syndrome (HFRS) in a large cohort of patients, and to identify factors associated with eosinophilia. RESULTS: Among 387 patients hospitalized for HFRS, 98 (25.3%) had eosinophilia. By univariate analysis, eosinophilia was significantly associated with more severe thrombocytopenia, high C-reactive protein level, white blood cell count and neutrophil count and lower nephrotoxic drug intake. As there was a collinearity between white blood cell count and C-reactive protein level, only C-reactive protein level with platelet count and nephrotoxic drug intake were entered in the multivariable analysis. Elevated C-reactive protein concentrations remained independently associated with eosinophilia. CONCLUSION: Eosinophilia during HFRS affects one quarter of patients, and supports the role of eosinophils in antiviral immunity against hantavirus infection.

Asymptomatic COVID-19 Adult Outpatients identified as Significant Viable SARS-CoV-2 Shedders.

Differential kinetics of RNA loads and infectious viral levels in the upper respiratory tract between asymptomatic and symptomatic SARS-CoV-2 infected adult outpatients remain unclear limiting recommendations that may guide clinical management, infection control measures and occupational health decisions. In the present investigation, 496 (2.8%) of 17,911 French adult outpatients were positive for an upper respiratory tract SARS-CoV-2 RNA detection by a quantitative RT-PCR assay, of which 180 (36.3%) were COVID-19 asymptomatic. Of these adult asymptomatic viral shedders, 75% had mean to high RNA viral loads (Ct values < 30) which median value was significantly higher than that observed in symptomatic subjects (P = 0.029), and 50.6% were positive by cell culture assays of their upper respiratory tract specimens. Our findings indicate that COVID-19 asymptomatic adult outpatients are significant viable SARS-CoV-2 shedders in their upper respiratory tract playing a major potential role as SARS-CoV-2 transmitters in various epidemiological transmission chains, promoting COVID-19 resurgence in populations.

Alveolar hemorrhage due to marijuana smoking using water pipe made with plastic bottle: case report and narrative review of the literature.

INTRODUCTION: We described a case of alveolar hemorrhage (AH) after marijuana smoking using a water pipe made with plastic bottle (bong) before making a narrative review of the literature. CASE REPORT: A 19-year-old male was admitted for hemoptysis and dyspnea evolving since the previous day. He smoked marijuana ten times a day using bongs. Computed tomography scan of the chest (chest CT-scan) evidenced ground glass opacities involving upper lobes with crazy-paving pattern. Bronchoalveolar lavage (BAL) yielded fluid becoming progressively bloody suggestive of AH. Screening of drug metabolites ruled out the presence of cocaine degradation products. Treatment with prednisone was prescribed and oxygen requirements decreased rapidly. The patient accepted to stop bongs, but kept on smoking marijuana using joints. He was asymptomatic 2 months later; all ground glass opacities had vanished. REVIEW OF THE LITERATURE: Four cases described exactly the same circumstances as ours. All were young male patients containing ground glass opacities with diffuse or bilateral pattern in their chest CT-scan. The explanation suggested by the authors of these cases was the potential concomitant inhalation of acid anhydrides derived from use of heated plastic bottle. No acid anhydrides were experimentally evidenced after thermodesorption of heated polyethylene terephthalate (PET) (in which a majority of plastic bottles are made) we performed, but other compounds were. E-cigarette, or vaping, product use-associated lung injuries cases share some chest CT-scan patterns with those of AH following bong use and we tried to draw a parallel between these two latter before discussing a physiopathological hypothesis.

A prospective, observational study of fidaxomicin use for Clostridioides difficile infection in France.

OBJECTIVE: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin. METHODS: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients. RESULTS: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported. CONCLUSIONS: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

Single-Dose 13-Valent Conjugate Pneumococcal Vaccine in People Living With HIV - Immunological Response and Protection.

Background: Patients living with HIV (PLHIV) are prone to invasive pneumococcal disease. The 13-valent conjugated pneumococcal vaccine (PCV13) is currently recommended for all PLHIV, followed in most guidelines by a 23-valent polysaccharide pneumococcal vaccine. Data are scarce concerning the immunological efficacy of PCV13 among PLHIV. Objective: To assess the immunological response at one month, and the immunological protection at 1-, 6-, and 12 months in PLHIV with a CD4 cell count above 200 cells/µl after a single dose of PCV13, as measured by both ELISA and opsonophagocytic assay (OPA). Methods: PLHIV with CD4 cell count >200 cells/µl were included. Specific IgG serum concentrations for eight serotypes by ELISA and seven serotypes by OPA were measured at baseline, 1-, 6-, and 12 months after the PCV13 vaccination. Global response was defined as a two-fold increase from baseline of specific IgG antibody levels (µg/ml) assayed by ELISA or as a four-fold increase in OPA titer from baseline, for at least five serotypes targeted by PCV13. Global protection was defined as an IgG-concentration ≥1 µg/ml by ELISA or as an opsonization titer ≥LLOQ by OPA for at least five tested serotypes targeted by PCV13. Factors associated with global response and global protection were assessed using logistic regression. Results: Of the 38 PLHIV included, 57.9% and 63.2% were global responders, 92.1% and 78.9% were globally protected at one month, and 64.7% and 55.9% were still protected at 12 months, by ELISA and OPA respectively. A CD4/CD8 ratio of >0.8 was significantly associated with a better global response by OPA (OR=6.11, p=0.02), and a CD4 nadir <200 was significantly associated with a poorer global response by ELISA (OR=0.22, p=0.04). A CD4 cell count nadir <200 and age over 50 years were associated with poorer global protection by OPA at M1 (OR=0.18, p=0.04) and M12 (OR= 0.15, p=0.02), respectively. Plasma HIV RNA viral load <40 copies/ml was significantly associated with a better global protection at M1 by ELISA and OPA (OR=21.33, p=0.025 and OR=8.40, p=0.04). Conclusion: Vaccination with PCV13 in these patients induced immunological response and protection at one month. At one year, more than half of patients were still immunologically protected.

Case Report: Could Artemisinin-Based Combination Therapy Prevent Occupational Malaria following Blood Exposure?

Postexposure prophylaxis using artemisinin-based combination therapy (ACT) was prescribed to a malaria-naive nurse who experienced an injury with a hollow needle previously used on a patient admitted for severe imported Plasmodium falciparum malaria (blood parasitemia 10.8%). Artemether-lumefantrine, four tablets twice daily for 3 days, was started 12 hours after exposure, and no side effects were reported. During the six following months, she only developed one episode of fever that was associated with pyelonephritis. Biological follow-up, based on blood smears, molecular biology, and serology, did not evidence P. falciparum malaria. This case suggests that ACT can prevent occupational P. falciparum malaria following needle-stick injury. We found evidence of only one other unpublished similar case where a Turkish resident doctor did not develop malaria after postexposure prophylaxis using ACT. Such a prophylaxis could be prescribed not only in case of occupational exposure to Plasmodium spp. in nonvector-borne laboratory-acquired infections but also following blood exposure in healthcare setting.

Obesity and Preoperative Anaemia as Independent Risk Factors for Sternal Wound Infection After Coronary Artery Bypass Graft Surgery with Pedicled (Non-Skeletonized) Internal Mammary Arteries: The Role of Thoracic Wall Ischemia?

PURPOSE: Obesity remains statistically associated with coronary artery disease, for which coronary artery bypass graft surgery (CABG) remains the standard of care. However, obesity is also associated with sternal wound infection (SWI) which is a severe complication of CABG despite advances in surgery and in infection prevention and control. Strategies to reduce the incidence of SWI are still being investigated, and we therefore conducted a retrospective study to revisit factors other than obesity associated with SWI after CABG. PATIENTS AND METHODS: Data were extracted from the medical records of 182 patients who underwent elective on-pump CABG using one or both pedicled internal mammary artery grafts in Reims University Hospital between May 2015 and May 2016. All preoperative or perioperative variables with a p value<0.10 in univariate analysis were entered into a stepwise logistic regression model. RESULTS: Among the 182 patients (145 male (79.6%), median age 68.0 [45.0-87.0] years), 138 (75.8%) underwent CABG using bilateral internal mammary artery grafts. Median BMI was 27.7 [18.7-50.5] kg/m2, and there were 51 (28.0%) and 79 (43.4%) patients with obesity and overweight, respectively. Twenty-three out of the 182 patients (12.6%) developed SWI. In-hospital mortality was not statistically different between patients with and without SWI but the median length of stay was (6.0 [2.0-38.0] versus 5.0[3.0-21.0] days in the intensive care unit, p=0.03, and 26.0 [9.0-134.0] versus 9.0 [7.0-51.0] days in hospital, p<0.0001). Obesity and preoperative anaemia were independently associated with SWI, as was the number of red blood cell (RBC) units transfused (OR 14.61 [2.64-80.75], OR 4.64 [1.61-13.34] and OR 1.27 [1.02-1.58], respectively). CONCLUSION: The independent association of SWI with the number of RBC units transfused and the existence of preoperative anaemia and obesity suggests a mechanism of thoracic wall ischemia in SWI after CABG, thus leaving insufficient perfusion of the thoracic wall in patients with obesity. Medical strategies are warranted to try to prevent this costly complication.