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This article, titled "EP04.01: First trimester diagnosis of cytomegalovirus trophoblastic infection using CMV-PCR: prediction of fetal CMV infection and symptoms at birth," discusses the use of CMV-PCR in diagnosing trophoblastic infection in pregnant women. The study aimed to determine the value of CMV-PCR in predicting fetal CMV infection and symptoms at birth. The results showed that CMV-PCR in trophoblast had a high negative predictive value for fetal infection and a high specificity and negative predictive value for symptomatic infection at birth. The study suggests that CMV-PCR on trophoblast can be a useful tool in diagnosing and predicting CMV infection in fetuses. [Extracted from the article]

This article discusses the challenges of predicting the postnatal outcomes of congenital cytomegalovirus (CMV) infection during pregnancy. The study evaluated the effectiveness of prenatal assessment, including different machine learning techniques, in predicting symptoms at birth and long-term sequelae. The research involved a large cohort of pregnant women who were referred for fetal infection following maternal infection in early pregnancy. The results suggest that prenatal imaging and early prenatal treatment, particularly in cases with mild prenatal findings, can influence the prognosis of infected fetuses. [Extracted from the article]

This article discusses a study that aimed to identify non-invasive markers for predicting fetal infection with cytomegalovirus (CMV) following maternal primary infection (MPI) before 14 weeks of gestation. The researchers conducted a retrospective study and found that the maximum trophoblast thickness (MTT) measured using three-dimensional ultrasound was significantly larger in cases where CMV was detected in the trophoblast and amniotic fluid. The study suggests that MTT could be a relevant and reproducible marker for diagnosing fetal CMV infection, but further research is needed to determine the threshold for MTT. The article was written by N. Bourgon, M. Jacquier, J. Fourgeaud, T. Guillerminot, L. Bussières, M. Leruez-Ville, and Y. Ville. [Extracted from the article]

In 23/30 patients (77%) and 14/17 (82%) of chilblains patients, COVID-19 was suspected in at least one first-degree relative and confirmed in four including two with chilblains. A clinical, histopathological and laboratory study of 19 consecutive Italian paediatric patients with chilblain-like lesions: lights and shadows on the relationship with COVID-19 infection. Serology was positive in only 1/16 chilblains patient among the 26 patients tested. [Extracted from the article]

Zika virus (ZIKV) infection during pregnancy can cause serious birth defects, including severe brain abnormalities. However, in congenital ZIKV infection, PCR analysis of AF has been reported to lack sensitivity because the ZIKV genome may be cleared from the AF, depending on the time elapsed since maternal primary infection[[1]]. Fetal Zika virus infection diagnosed by metagenomic next-generation sequencing of amniotic fluid. [Extracted from the article]

Background: The treatment of congenital cytomegalovirus (CMV) infection is usually administered to neonates after birth; however, it can be anticipated during the prenatal period by treating pregnant women in order to reduce the severity of the congenital disease. The most commonly used treatment for CMV during pregnancy is valaciclovir; however, valganciclovir has a higher potency against CMV and is the first choice for neonates with congenital CMV disease., Objectives: We investigated neonatal and maternal safety of tertiary prevention in infected fetuses showing ultrasound features of infection using valganciclovir., Methods: Retrospective cohort study of pregnant women and their symptomatic infected fetuses taking valganciclovir, 3 × 450 mg per day. All fetuses presented at least one prenatal feature on ultrasound. We assessed fetal/neonatal and maternal safety, as well as neonatal efficacy of treatment. The main outcome was neutropenia. Secondary outcomes included other haematological side effects, symptoms at birth and neonatal CMV-PCR was positive., Results: Seventeen women with singleton pregnancies received valganciclovir from a median (IQR) of 27.1 (26.0-30.3) to 11.6 (6.5-12.9) weeks of gestation. No neonatal neutropenia was reported. One pregnancy was terminated for severe features. Three newborns (18%) were asymptomatic at birth, including one with negative CMV-PCR from blood and saliva. CMV-PCR was positive for 12/13 symptomatic newborns, with a median (IQR) log10 viral load of 3.36 (3.30-4.20), 4.03 (1.75-4.27) and 3.04 (0.00-3.40) log10 copies/mL in blood, urine and saliva, respectively., Conclusions: Tertiary prevention by valganciclovir appears to be well tolerated for both fetus and mother. However, more extensive trials accompanied by long-term follow-up are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Enteric viruses are the main cause of acute gastroenteritis worldwide with a significant morbidity and mortality, especially among children and aged adults. Some enteric viruses also cause disseminated infections and severe neurological manifestations such as poliomyelitis. Protective immunity against these viruses is not well understood in humans, with most knowledge coming from animal models, although the development of poliovirus and rotavirus vaccines has extended our knowledge. In a classical view, innate immunity involves the recognition of foreign DNA or RNA by pathogen recognition receptors leading to the production of interferons and other inflammatory cytokines. Antigen uptake and presentation to T cells and B cells then activate adaptive immunity and, in the case of the mucosal immunity, induce the secretion of dimeric IgA, the more potent immunoglobulins in viral neutralization. The study of Inborn errors of immunity (IEIs) offers a natural opportunity to study nonredundant immunity toward pathogens. In the case of enteric viruses, patients with a defective production of antibodies are at risk of developing neurological complications. Moreover, a recent description of patients with low or absent antibody production with protracted enteric viral infections associated with hepatitis reinforces the prominent role of B cells and immunoglobulins in the control of enteric virus., (© 2024 The Author(s). Immunological Reviews published by John Wiley & Sons Ltd.)

FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors. Counts of B cells, monocytes, and DCs were low in the patients' blood, whereas the other blood subsets, including NK cells, were affected only moderately, if at all. The patients had normal counts of Langerhans cells (LCs) and dermal macrophages in the skin but lacked dermal DCs. Thus, FLT3L is required for B cell and DC development in mice and humans. However, unlike its murine counterpart, human FLT3L is required for the development of monocytes but not NK cells., Competing Interests: Declaration of interests J.-L.C. serves on the scientific advisory boards of ADMA Biologics Inc., Kymera Therapeutics, and Elixiron Immunotherapeutics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Approximately 20% of neonates with congenital cytomegalovirus (cCMV) develop long-term sequelae. The ability to accurately predict long-term outcomes as early as the neonatal period would help to provide for appropriate parental counseling and treatment indications. With this study, we aimed to identify neonatal predictive markers of cCMV long-term outcomes., Methods: As this study's subjects, we chose neonates diagnosed with cCMV in 13 hospitals throughout France recruited from 2013 to 2017 and evaluated for at least 2 years with thorough clinical, audiology, and imaging evaluations and psychomotor development tests., Results: A total of 253 neonates were included, and 3 were later excluded because of the identification of a genetic disorder. A total of 227 were followed up for 2 years: 187/227 (82%) and 34/227 (15%) were infected after a maternal primary or nonprimary infection, respectively, 91/227 (40%) were symptomatic at birth, and 44/227 (19%) had cCMV sequelae. Maternal primary infection in the first trimester was the strongest prognosis factor (odds ratio = 38.34 [95% confidence interval, 5.02-293], P < .001). A predictive model of no risk of sequelae at 2 years of age according to normal hearing loss at birth, normal cerebral ultrasound, and normal platelet count had 98% specificity, 69% sensitivity, and 0.89 area under the curve (95% confidence interval, 0.83-0.96)., Conclusions: In the studied population, children with normal hearing at birth, normal platelet count at birth, and a normal cranial ultrasound had no risk of neurologic sequelae and a low risk of delayed unilateral sensorineural hearing loss. The use of this model based on readily available neonatal markers should help clinicians establish a personalized care pathway for each cCMV neonate., (Copyright © 2024 by the American Academy of Pediatrics.)

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17-20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families., Competing Interests: MLV reports receiving support for attending meetings by BioMérieux and Altona outside the submitted work. MLV reports payment made to her institution for presentation/lecture by Diasorin, Abbott Molecular and Roche Diagnostic outside the submitted work. DBG received Grant from the Spanish Ministry of Science and Innovation. ISCIII and Fondos FEDER (EU) outside the submitted work and received Honoraria for lectures from the Medscape, outside the submitted work. JF received honoraria for poster presentation by Abbott GmbH, outside the submitted work. CJ received consulting fees from Moderna, outside the submitted work; Participated on a Data Safety Monitoring Board or Advisory Board of Moderna, outside the submitted work; Is Co-director of the European Congenital CMV Initiative; Her institution received payment for clinical trials by Moderna, outside the submitted work. HL participated on advisory board for the Study of Zidovudine in children with Aicadri-Goutiere Syndrome, outside the submitted work and she is Trustee of European Society For Paediatric Infectious Diseases (ESPID). VP institution received honoraria for lectures from MSD and Pfizer, outside the submitted work and received support for attending a meeting (ESPID 2023) from Pfizer. PV is president and board-member of the European Congenital CMV Initiative. AV is participating in the Advisory Council European Society of Virology. The rest author of the authors declare no conflict of interest., (© 2024 The Author(s).)

Background: Metagenomic next-generation sequencing (mNGS) allows untargeted identification of a broad range of pathogens, including rare or novel microorganisms. Despite the recognition of mNGS as a valuable diagnostic tool for infections, the most relevant indications for this innovative strategy remain poorly defined. We aimed to assess the determinants of positivity and clinical utility of mNGS., Methods: In this observational study, we prospectively performed short-read shotgun metagenomics analysis as a second-line test (in cases of negative first-line test or when the symptoms were not fully explained by initial positive results) or as a first-line test in life-threatening situations requiring urgent non-targeted pathogen identification at the Necker-Enfants Malades Hospital (Paris, France). All sample types, clinical indications, and patient populations were included. Samples were accompanied by a mandatory form completed by the senior clinician or pathologist, on which the clinical level of suspected infection (defined as high or low) was indicated. We assessed the variables (gender, age, immune status, initial suspicion of infection, indication, and sample type) associated with mNGS pathogen detection using odds ratios (ORs) from multivariate logistic regression. Additional investigations were carried out using specific PCR or culture techniques, to confirm positive mNGS results, or when infectious suspicion was particularly high despite a negative mNGS result., Findings: Between Oct 29, 2019, and Nov 7, 2022, we analysed 742 samples collected from 523 patients. The initial suspicion of infection was either high (n=470, 63%) or low (n=272, 37%). Causative or possibly causative pathogens were detected in 117 (25%) samples from patients with high initial suspicion of infection, versus nine (3%) samples analysed to rule out infection (OR 9·1, 95% CI 4·6-20·4; p<0·0001). We showed that mNGS had higher odds of detecting a causative or possibly causative pathogenic virus on CNS biopsies than CSF samples (4·1, 1·7-10·7; p=0·0025) and in samples from immunodeficient compared with immunocompetent individuals (2·4, 1·4-4·1; p=0·0013). Concordance with conventional confirmatory tests results was 103 (97%) of 106, when mNGS detected causative or possibly causative pathogens. Altogether, among 231 samples investigated by both mNGS and subsequent specific tests, discordant results were found in 69 (30%) samples, of which 58 (84%) were mNGS positive and specific tests negative, and 11 (16%) mNGS negative and specific tests positive., Interpretation: Major determinants of pathogen detection by mNGS are immune status and initial level of suspicion of infection. These findings will contribute, along with future studies, to refining the positioning of mNGS in diagnostic and treatment decision-making algorithms., Funding: Necker-Enfants Malades Hospital and Institut Pasteur., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: CMV serology screening in the first trimester pregnancy is based on IgG and IgM testing followed by IgG avidity in cases with positive IgM. However, the sensitivity of this strategy to diagnose maternal primary infection has been questioned. The objective of the study was to compare this strategy 1 with a strategy 2 consisting of running avidity test on all samples with positive IgG (ignoring IgM results) using fully automated current generation CMV IgG, IgM and IgG avidity assays., Population and Methods: 1516 consecutive pregnant women between 12 and 14 weeks were screened in one maternity. Strategy 1 was done prospectively with LIAISON® CMV IgG II and LIAISON® CMV IgM II, followed by LIAISON® CMV IgG Avidity II and VIDAS® CMV IgG avidity II testing in cases with positive or equivocal IgM. Strategy 2 was done retrospectively on the same population and consisted of running avidity with the LIAISON® CMV IgG Avidity II in all samples with positive IgG., Results: The sensitivity to diagnose a confirmed or a possible maternal primary infection in the first trimester was 91.6 % and 83 % for strategy 1 and 2 respectively (p > 0.99). Strategy 1 missed one possible primary infection and strategy 2 missed 2 confirmed primary infection. Inconclusive results happened in 0 and 0.7 % of samples with strategy 1 and 2 respectively., Conclusion: This study suggests that strategy 1 has better sensitivity and practicability than strategy 2. However, to achieve a good performance with strategy 1, using highly sensitive IgM assay is mandatory., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marianne Leruez-Ville reports non-financial support from BioMérieux, non-financial support from Abbott, non-financial support from Diasorin outside the submitted work. Yves Ville reports non-financial support from GE Medical, non-financial support from Ferring SAS, non-financial support from Siemens Health care outside the submitted work. Jacques Fourgeaud, Chieu-An Nguyen and Tiffany Guilleminot declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Metagenomic next-generation sequencing (mNGS) was used to assess patients with primary or secondary immune deficiencies (PIDs and SIDs) who presented with immunopathological conditions related to immunodysregulation., Methods: Thirty patients with PIDs or SIDs who presented with symptoms related to immunodysregulation and 59 asymptomatic patients with similar PIDs or SIDs were enrolled. mNGS was performed on organ biopsy. Specific Aichi virus (AiV) reverse-transcription polymerase chain reaction (RT-PCR) was used to confirm AiV infection and screen the other patients. In situ hybridization (ISH) assay was done on AiV-infected organs to identify infected cells. Virus genotype was determined by phylogenetic analysis., Results: AiV sequences were detected using mNGS in tissue samples of 5 patients and by RT-PCR in peripheral samples of another patient, all of whom presented with PID and long-lasting multiorgan involvement, including hepatitis, splenomegaly, and nephritis in 4 patients. CD8+ T-cell infiltration was a hallmark of the disease. RT-PCR detected intermittent low viral loads in urine and plasma from infected patients but not from uninfected patients. Viral detection stopped after immune reconstitution obtained by hematopoietic stem cell transplantation. ISH demonstrated the presence of AiV RNA in hepatocytes (n = 1) and spleen tissue (n = 2). AiV belonged to genotype A (n = 2) or B (n = 3)., Conclusions: The similarity of the clinical presentation, the detection of AiV in a subgroup of patients suffering from immunodysregulation, the absence of AiV in asymptomatic patients, the detection of viral genome in infected organs by ISH, and the reversibility of symptoms after treatment argue for AiV causality., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Allogenic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT) are potentially curative treatments for severe combined immunodeficiency (SCID). Late-onset posttreatment manifestations (such as persistent hepatitis) are not uncommon., Objective: We sought to characterize the prevalence and pathophysiology of persistent hepatitis in transplanted SCID patients (SCIDH+) and to evaluate risk factors and treatments., Methods: We used various techniques (including pathology assessments, metagenomics, single-cell transcriptomics, and cytometry by time of flight) to perform an in-depth study of different tissues from patients in the SCIDH+ group and corresponding asymptomatic similarly transplanted SCID patients without hepatitis (SCIDH-)., Results: Eleven patients developed persistent hepatitis (median of 6 years after HSCT or GT). This condition was associated with the chronic detection of enteric viruses (human Aichi virus, norovirus, and sapovirus) in liver and/or stools, which were not found in stools from the SCIDH- group (n = 12). Multiomics analysis identified an expansion of effector memory CD8 + T cells with high type I and II interferon signatures. Hepatitis was associated with absence of myeloablation during conditioning, split chimerism, and defective B-cell function, representing 25% of the 44 patients with SCID having these characteristics. Partially myeloablative retransplantation or GT of patients with this condition (which we have named as "enteric virus infection associated with hepatitis") led to the reconstitution of T- and B-cell immunity and remission of hepatitis in 5 patients, concomitantly with viral clearance., Conclusions: Enteric virus infection associated with hepatitis is related to chronic enteric viral infection and immune dysregulation and is an important risk for transplanted SCID patients with defective B-cell function., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

In March 2022, a 61-year-old woman in France who had received a heart-lung transplant sought treatment with chronic hepatitis mainly characterized by increased liver enzymes. After ruling out common etiologies, we used metagenomic next-generation sequencing to analyze a liver biopsy sample and identified an unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). We found no other viral or bacterial sequences. HCirV-1 shared 70% amino acid identity with the closest known viral sequences. The viral genome was undetectable in blood samples from 2017-2019, then became detectable at low levels in September 2020 and peaked at very high titers (10 10 genome copies/mL) in January 2022. In March 2022, we found >10 8 genome copies/g or mL in the liver and blood, concomitant with hepatic cytolysis. We detected HCirV-1 transcripts in 2% of hepatocytes, demonstrating viral replication and supporting the role of HCirV-1 in liver damage.

Objective: To evaluate cytomegalovirus (CMV) viral load dynamics in blood and saliva during the first 2 years of life in symptomatic and asymptomatic infected infants and to identify whether these kinetics could have practical clinical implications., Study Design: The Cymepedia cohort prospectively included 256 congenitally infected neonates followed for 2 years. Whole blood and saliva were collected at inclusion and months 4 and 12, and saliva at months 18 and 24. Real-time CMV polymerase chain reaction (PCR) was performed, results expressed as log 10 IU/mL in blood and in copies per milliliter in saliva., Results: Viral load in saliva progressively decreased from 7.5 log 10 at birth to 3.3 log 10 at month 24. CMV PCR in saliva was positive in 100% and 96% of infants at 6 and 12 months, respectively. In the first month of life, neonatal saliva viral load of less than 5 log 10 was related to a late CMV transplacental passage. Detection in blood was positive in 92% of neonates (147/159) in the first month of life. No viral load threshold values in blood or saliva could be associated with a high risk of sequelae. Neonatal blood viral load of less than 3 log 10 IU/mL had a 100% negative predictive value for long-term sequelae., Conclusions: Viral loads in blood and saliva by CMV PCR testing in congenital infection fall over the first 24 months. In this study of infants affected mainly after primary maternal infection during pregnancy, all salivary samples were positive in the first 6 months of life and sequelae were not seen in infants with neonatal blood viral load of less than 3 log 10 IU/mL., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Renal arcuate vein thrombosis (RAVT) is a rare and recently recognized cause of acute kidney injury (AKI) in young adults. However, the precise incidence and underlying pathophysiologic mechanisms leading to AKI in these patients remain elusive., Methods: This study included all patients who underwent a kidney biopsy over a 40-month period sent to the pathology department of Necker-Enfants Malades Hospital, with evidence of RAVT. We performed coagulation tests, genetic testing for thrombophilia, complete urine toxicologic screening and kidney metagenomic sequencing to identify an underlying cause of thrombosis., Results: We report five pediatric cases of RAVT discovered on kidney biopsy performed in the setting of unexplained AKI. Investigations did not reveal an underlying cause of thrombosis but only a significant nonsteroidal anti-inflammatory drugs (NSAIDs) use was reported in 4/5 patients, supporting a potential link between NSAIDs use and RAVT. By performing metagenomic sequencing on kidney biopsy samples, we detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the kidney of one patient. These results suggest that systemic SARS-CoV-2 infection may also be a key contributing factor of renal thrombosis, particularly by inducing potential endothelial disruption., Conclusions: In conclusion, RAVT-induced AKI appears to be a multiple hit-mediated disease in which NSAIDs consumption and viral infection such as SARS-CoV-2 may be crucial contributing factors. These findings may have significant public health implications given the prevalence of NSAIDs use in the general population. Increased awareness and additional study of future cases may lead to a better understanding of this rare cause of AKI in children and young adults., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: Cytomegalovirus (CMV) is the most frequent cause of congenital infection and ≈20% of all infected neonates present or will develop sensorineural hearing loss. Targeted congenital CMV (cCMV) screening in newborns who failed universal newborn hearing screening has been proposed as a strategy to identify neonates with both hearing loss and cCMV infection who could benefit from antiviral treatment implemented within the first month of life., Objectives: To evaluate the feasibility and performance of cCMV targeted screening in a French setting., Methods: Neonates were recruited in 5 maternity centers in greater Paris. A saliva sample for CMV polymerase chain reaction (PCR) testing was collected in neonates who failed newborn hearing screening. Outcomes including CMV PCR result and confirmation of hearing loss by an otorhinolaryngologist specialist were documented., Results: Two-hundred thirty-six newborns were included and a saliva sample was collected in 98% (231/236) of them. The result of CMV PCR was available at a median of 9 days (7-10 days) of life and in 96% of cases within the first month of life. Two neonates were infected with CMV. The result of the otorhinolaryngologist assessment was available in 75% (178/236) of cases at a median of 16 days (9-26 days). Hearing loss was confirmed in 2.8% (5/178). The 2 infected neonates had hearing loss confirmed at 5 and 8 days of life and were treated with valganciclovir at days 9 and 16, respectively., Conclusions: The result of this study confirms that targeted cCMV screening is feasible in these French settings., Competing Interests: Y.V. declares receiving fees for lectures from General Electric outside this work. M.L.-V. declares having received fees paid to her institution for expertise of diagnosis kits and for lectures from BioMérieux and Diasorin outside this work and for participating to conferences from Abbott and Roche. The other authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Enteroviruses (EV) are the most frequent cause of acute meningitis worldwide, and regularly responsible for outbreaks. Human parechoviruses (PeV) are associated with sepsis and meningitis in young infants. In Mayotte, a French department located in the Comoros archipelago, EVs and PeVs are not part of the routine screening of cerebrospinal fluids (CSFs) of patients with meningitis. Consequently, no data is available on EV or PeV epidemiology., Aim: Assess the need for EV and PeV diagnosis in Mayotte., Methods: CSFs collected between March and June 2019 from patients addressed to Mayotte Hospital were retrospectively screened for EV and PeV by PCR. If positive for EV, genotyping was attempted., Results: EV and PeV RT-PCR were performed on 122/263 (46%) CSFs (45 adults, 77 children). EV meningitis was diagnosed in 16/77 children (21%) with a median age of 32 days (8-62). One 30-days-aged infant presented with a PeV infection. Fever was reported in 94% cases (16/17), followed by gastrointestinal disorders in 29% cases (5/17). EV genotyping achieved identification for 10/16 (63%) EV-positive samples. Four different EV types were identified: Echovirus 16 (E-16, n = 6), EV-B100 (n = 2), and E-14 and E-18 (n = 1, each)., Conclusion: EV/PeV prevalence of 14% highlights the importance of implementing this diagnosis which can impact duration of hospitalization and administration of antibiotics thus reducing risk of antimicrobial resistance. Surveillance of circulating EV types is needed to understand the range of enteroviruses detected in meningitis cases in places that have been underrepresented in enterovirus surveillance studies., (Copyright © 2022. Published by Elsevier B.V.)

This communication described how the Coris BioConcept COVID-19 Ag Respi-Strip test (Coris-Ag) was implemented in the workflow of our clinical microbiology laboratory for COVID-19 diagnosis. The diagnostic performance statistics (sensitivity, specificity) of the Coris-Ag were evaluated against a gold standard, the RealStar SARS-CoV-2 RT-PCR kit 1.0. Additionally, the effect of reading the Coris-Ag results at 30 min was compared to reading at 15 min. The Coris-Ag was performed on a total of 294 patients during two periods; 158 patients were tested during period 1 at the peak of the pandemic (April 6th to April 10th 2020) which returned a positivity rate of 17.1 %, and 136 patients during period 2 (April 12th to April 16th 2020) which returned a positivity rate of 11 %. Compared to the RT-PCR, the 15-minute Coris-Ag readings resulted in a sensitivity of 59.3 % with a 100 % specificity for the period 1 patients (n = 158) while the sensitivity decreased to 20 % for the period 2 patients (n = 136). The overall sensitivity was 38.1 % for both periods (n = 294). The corresponding 30-minute readings produced a 7 % increase in sensitivity with a specificity of 100 % (n = 294). The sensitivity of the strip test (15-min reading) for high viral loads (Ct <25) was 84.6 %., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the standard diagnostic test of coronavirus disease 2019. Our objectives were to assess, in real-life conditions, the diagnostic accuracy of a nasopharyngeal point-of-care antigen (Ag) test and of saliva NAAT for detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in ambulatory care. This was a prospective cohort study from 19 October through 18 December 2020 in two community COVID-19 screening centers in Paris, France. Two nasopharyngeal swabs and one saliva sample were simultaneously collected. Diagnostic accuracies of nasopharyngeal Ag testing and of three saliva NAAT methods were assessed as compared to nasopharyngeal NAAT. A total of 1452 ambulatory children and adults were included. Overall, 129/1443 (9%) participants tested positive on nasopharyngeal NAAT (102/564 [18%] in symptomatic and 27/879 [3%] in asymptomatic participants). Sensitivity was 94%, 23%, 96%, and 94% for the three different protocols of saliva NAAT and for the nasopharyngeal Ag test, respectively. Estimates of specificity were above 95% for all methods. Diagnostic accuracy was similar in symptomatic and asymptomatic individuals. Diagnostic accuracy of nasopharyngeal Ag testing and of saliva NAAT is similar to that of nasopharyngeal NAAT, subject to compliance with specific protocols for saliva. Registration number: NCT04578509., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Since the beginning of the COVID-19 pandemic, other respiratory illnesses decreased worldwide. This study described the consequences of public health measures on respiratory syncytial virus (RSV) severe infections in France, where an interseasonal resurgence of RSV occurred recently. All patients admitted to Necker Hospital (Paris) between August 2018 and April 2021 with a diagnosis of RSV-associated acute lung respiratory infection (ALRI) were enrolled. Characteristics of subjects with RSV-associated ALRI in 2020/2021 were compared to those infected during the two previous outbreaks. Overall, 664 inpatients were diagnosed with RSV-associated ALRI: 229, 183, and 252 during the 2018/2019, 2019/2020, and 2020/2021 outbreaks, respectively. During autumn 2020, a national lockdown began in France but schools remained open. A 3-month delayed RSV epidemic occurred at the end of this lockdown. Compared to previous outbreaks, the 2020/2021 epidemics involved more children aged 6 to 11 months (25.8% versus 13.1%, p < 0.0001), but less infants aged < 6 months (41.3% versus 56.6%, p < 0.0001) and less adults (0.0 versus 2.7%, p < 0.0001). Shorter length of stay at hospital, less frequent requirement of admission to intensive care unit, use of non-invasive ventilation, and/or high-flow nasal oxygen were observed in 2020/2021 than during previous epidemics (p < 0.0001). Delayed RSV outbreak was associated with more hospitalizations for ALRI, higher age of pediatric inpatients, but milder median clinical phenotype. Reinforced public health measures (even while keeping nurseries and schools open with mandatory face masks since six years of age) could impact, at least transiently, the burden of RSV-related hospitalizations., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The dynamics of SARS-CoV-2 alpha variant shedding and immune responses at the nasal mucosa remain poorly characterised., Methods: We measured infectious viral release, antibodies and cytokines in 426 PCR+ nasopharyngeal swabs from individuals harboring non-alpha or alpha variants., Findings: With both lineages, viral titers were variable, ranging from 0 to >10 6  infectious units. Rapid antigenic diagnostic tests were positive in 94% of samples with infectious virus. 68 % of individuals carried infectious virus within two days after onset of symptoms. This proportion decreased overtime. Viable virus was detected up to 14 days. Samples containing anti-spike IgG or IgA did not generally harbor infectious virus. Ct values were slightly but not significantly lower with alpha. This variant was characterized by a fast decrease of infectivity overtime and a marked release of 13 cytokines (including IFN-b, IP-10 and IL-10)., Interpretation: The alpha variant displays modified viral decay and cytokine profiles at the nasopharyngeal mucosae during symptomatic infection., Funding: This retrospective study has been funded by Institut Pasteur, ANRS, Vaccine Research Institute, Labex IBEID, ANR/FRM and IDISCOVR, Fondation pour la Recherche Médicale., Competing Interests: Declaration of Competing Interest L.G., I.S., T.B., F.G.-B., and O.S. have a patent US 63/020,063 entitled “S-Flow: a FACS-based assay for serological analysis of SARS-CoV2 infection” pending. The other authors have no conflict of interests to disclose., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Rapid identification of SARS-CoV-2-infected individuals is a cornerstone for the control of virus spread. The sensitivity of SARS-CoV-2 RNA detection by RT-PCR is similar in saliva and nasopharyngeal swabs. Rapid molecular point-of-care tests in saliva could facilitate, broaden and speed up the diagnosis. We conducted a prospective study in two community COVID-19 screening centers to evaluate the performances of a CE-marked RT-LAMP assay (EasyCoV) designed for the detection of SARS-CoV2 RNA from fresh saliva samples, compared to nasopharyngeal RT-PCR, to saliva RT-PCR and to nasopharyngeal antigen testing. Overall, 117 of the 1718 participants (7%) tested positive with nasopharyngeal RT-PCR. Compared to nasopharyngeal RT-PCR, the sensitivity and specificity of the RT-LAMP assay in saliva were 34% and 97%, respectively. The Ct values of nasopharyngeal RT-PCR were significantly lower in the 40 true positive subjects with saliva RT-LAMP (Ct 25.9) than in the 48 false negative subjects with saliva RT-LAMP (Ct 28.4) (p = 0.028). Considering six alternate criteria for reference tests, including saliva RT-PCR and nasopharyngeal antigen, the sensitivity of saliva RT-LAMP ranged between 27 and 44%. The detection of SARS-CoV-2 in crude saliva samples with an RT-LAMP assay had a lower sensitivity than nasopharyngeal RT-PCR, saliva RT-PCR and nasopharyngeal antigen testing.Registration number: NCT04578509., (© 2021. The Author(s).)

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

OBJECTIVES Congenital cytomegalovirus infection (cCMV) affects around 3400 newborns each year in France, of whom 700 will develop sequelae, primarily sensorineural hearing loss. Our objectives were (1) to evaluate incidence of cCMV in two French departments located in the Indian Ocean: Mayotte and La Reunion, and (2) evaluate interest and feasibility/acceptability of universal screening of cCMV at birth. MATERIAL AND METHODS We implemented a universal neonatal CMV screening in Mayotte during 7 months in 2019 and in La Reunion during one month in March 2020. Saliva swabs were collected in the first three days of life, and tested for CMV DNA by PCR. A short survey allowed evaluating whether this screening is acceptable and feasible. RESULTS: A total of 1026 newborns were screened: 854 in Mayotte and 172 in La Reunion. In Mayotte, cCMV incidence was evaluated at a minimum of 1.6 % (95 % CI 0.94-2.81). In La Reunion, cCMV incidence was evaluated at a minimum of 1.2 % (95 % CI -0.20-4.57). All cCMV infants were born to mothers with non-primary CMV infection. Only 0.7 % parents refused the screening. CONCLUSIONS cCMV incidence in Mayotte and La Reunion is higher than in metropolitan France. This diagnosis should not be overlooked, especially since the time dedicated to screening and its feeling by the parents seem to be acceptable., (Copyright © 2021. Published by Elsevier B.V.)

In this case-control study on 564 healthcare workers of a university hospital in Paris (France), contacts without protection with coronavirus disease 2019 (COVID-19) patients or with colleagues were associated with infection with severe acute respiratory syndrome coronavirus 2, whereas working in a COVID-dedicated unit and having children kept in childcare facilities were not., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Healthcare workers (HCWs) have paid a heavy toll during the coronavirus disease 2019 (COVID-19) outbreak. Routes of transmission remain to be fully understood., Methods: This prospective study compared a 1500-bed adult and 600-bed pediatric setting of a tertiary-care university hospital located in central Paris. From 24 February until 10 April 2020, all symptomatic HCWs were screened for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on a nasopharyngeal swab. HCWs screened positive were questioned on their profession, symptoms, and occupational and nonoccupational exposures to SARS-CoV-2., Results: Among 1344 HCWs tested, 373 were positive (28%) and 336 (90%) corresponding questionnaires were completed. Three hospitalizations and no deaths were reported. Most HCWs (70%) had patient-facing occupational activities (22% in COVID-19 dedicated units). The total number of HCW cases peaked on 23 March, then decreased slowly, concomitantly with a continuous increase of compliance to preventive measures (including universal medical masking and personal protective equipment [PPE] for direct care to COVID-19 patients). Attack rates were of 3.2% and 2.3% in the adult and pediatric settings, respectively (P = .0022). In the adult setting, HCWs more frequently reported exposure to COVID-19 patients without PPE (25% vs 15%, P = .046). Report of contacts with children attending out-of-home care facilities dramatically decreased over the study period., Conclusions: Universal masking, reinforcement of hand hygiene, and PPE with medical masks for patients' care allowed protection of HCWs and containment of the outbreak. Residual transmissions were related to persistent exposures with undiagnosed patients or colleagues and not to contacts with children attending out-of-home care facilities., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)