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  1. Article ; Online: Human Circovirus is not detected in plasma pools for fractionation.

    Pérot, Philippe / Da Rocha, Nicolas / Farcet, Maria R / Kreil, Thomas R / Eloit, Marc

    Transfusion

    2023  Volume 64, Issue 1, Page(s) 16–18

    Abstract: Background: Human Circovirus 1 and 2 were recently described in a French hepatitis case and in two Chinese drug users. Because of its small size and presumable high resistance to both inactivation and removal by nanofilters, such viruses-if determined ... ...

    Abstract Background: Human Circovirus 1 and 2 were recently described in a French hepatitis case and in two Chinese drug users. Because of its small size and presumable high resistance to both inactivation and removal by nanofilters, such viruses-if determined to be even pathogenic-should be considered with respect to the safety of plasma derivatives. We, therefore, investigated the prevalence and titer of these viruses in plasma pools before fractionation.
    Methods and materials: We tested for the presence of Human Circovirus 1 and 2 by qPCR in 48 plasma pools derived from healthy donors from Europe, USA, and Japan, corresponding to more than 200,000 plasma donations.
    Results: We did not detect the presence of Human Circovirus 1 and 2 in any of the plasma pools, with a limit of detection of 300-600 genome copies per mL of plasma.
    Conclusions: These results indicate that high levels of circovirus are not widely prevalent in such donations.
    MeSH term(s) Humans ; Circovirus/genetics ; Plasma ; Europe ; Japan
    Language English
    Publishing date 2023-11-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.17604
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    Zs.A 284: Show issues Location:
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  2. Article ; Online: Circovirus Hepatitis Infection in Heart-Lung Transplant Patient, France.

    Pérot, Philippe / Fourgeaud, Jacques / Rouzaud, Claire / Regnault, Béatrice / Da Rocha, Nicolas / Fontaine, Hélène / Le Pavec, Jérôme / Dolidon, Samuel / Garzaro, Margaux / Chrétien, Delphine / Morcrette, Guillaume / Molina, Thierry Jo / Ferroni, Agnès / Leruez-Ville, Marianne / Lortholary, Olivier / Jamet, Anne / Eloit, Marc

    Emerging infectious diseases

    2023  Volume 29, Issue 2, Page(s) 286–293

    Abstract: 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 ... ...

    Abstract 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
    MeSH term(s) Female ; Humans ; Middle Aged ; Circovirus/genetics ; Heart-Lung Transplantation ; Genome, Viral ; Hepatitis ; Hepatitis A
    Language English
    Publishing date 2023-01-03
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 1380686-5
    ISSN 1080-6059 ; 1080-6040
    ISSN (online) 1080-6059
    ISSN 1080-6040
    DOI 10.3201/eid2902.221468
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  3. Article: Renal arcuate vein thrombosis-induced acute kidney injury: a rare multiple-Hit-mediated disease.

    Pardinhas, Clara / Filipe, Rui / Vergnaud, Paul / Grapin, Mathilde / Ferrière, Elsa / Jamet, Anne / Fourgeaud, Jacques / Da Rocha, Nicolas / Pérot, Philippe / Boyer, Olivia / Rabant, Marion / Van Huyen, Jean-Paul Duong / Isnard, Pierre

    Clinical kidney journal

    2022  Volume 16, Issue 2, Page(s) 367–373

    Abstract: 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 ... ...

    Abstract 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.
    Language English
    Publishing date 2022-11-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2655800-2
    ISSN 2048-8513 ; 2048-8505
    ISSN (online) 2048-8513
    ISSN 2048-8505
    DOI 10.1093/ckj/sfac244
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  4. Article ; Online: Performance of clinical metagenomics in France: a prospective observational study.

    Fourgeaud, Jacques / Regnault, Béatrice / Ok, Vichita / Da Rocha, Nicolas / Sitterlé, Émilie / Mekouar, Meryem / Faury, Hélène / Milliancourt-Seels, Catherine / Jagorel, Florence / Chrétien, Delphine / Bigot, Thomas / Troadec, Éric / Marques, Isabelle / Serris, Alexandra / Seilhean, Danielle / Neven, Bénédicte / Frange, Pierre / Ferroni, Agnès / Lecuit, Marc /
    Nassif, Xavier / Lortholary, Olivier / Leruez-Ville, Marianne / Pérot, Philippe / Eloit, Marc / Jamet, Anne

    The Lancet. Microbe

    2023  Volume 5, Issue 1, Page(s) e52–e61

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; France/epidemiology ; Prospective Studies ; Paris ; High-Throughput Nucleotide Sequencing ; Affect
    Language English
    Publishing date 2023-12-01
    Publishing country England
    Document type Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-5247
    ISSN (online) 2666-5247
    DOI 10.1016/S2666-5247(23)00244-6
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  5. Article ; Online: Chronic Aichi Virus Infection As a Cause of Long-Lasting Multiorgan Involvement in Patients With Primary Immune Deficiencies.

    Fourgeaud, Jacques / Lecuit, Mathilde M / Pérot, Philippe / Bruneau, Julie / Regnault, Beatrice / Da Rocha, Nicolas / Bessaud, Mael / Picard, Capucine / Jeziorski, Éric / Fournier, Benjamin / Levy, Romain / Marçais, Ambroise / Blanche, Stéphane / Frange, Pierre / Fischer, Alain / Cavazzana, Marina / Ferroni, Agnès / Jamet, Anne / Leruez-Ville, Marianne /
    Eloit, Marc / Neven, Bénédicte

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2023  Volume 77, Issue 4, Page(s) 620–628

    Abstract: 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 ... ...

    Abstract 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.
    MeSH term(s) Humans ; Kobuvirus/genetics ; Phylogeny ; Patients ; Primary Immunodeficiency Diseases ; Virus Diseases
    Language English
    Publishing date 2023-04-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciad237
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  6. Article ; Online: Late-onset enteric virus infection associated with hepatitis (EVAH) in transplanted SCID patients.

    Riller, Quentin / Fourgeaud, Jacques / Bruneau, Julie / De Ravin, Suk See / Smith, Grace / Fusaro, Mathieu / Meriem, Samy / Magerus, Aude / Luka, Marine / Abdessalem, Ghaith / Lhermitte, Ludovic / Jamet, Anne / Six, Emmanuelle / Magnani, Alessandra / Castelle, Martin / Lévy, Romain / Lecuit, Mathilde M / Fournier, Benjamin / Winter, Sarah /
    Semeraro, Michaela / Pinto, Graziella / Abid, Hanène / Mahlaoui, Nizar / Cheikh, Nathalie / Florkin, Benoit / Frange, Pierre / Jeziorski, Eric / Suarez, Felipe / Sarrot-Reynauld, Françoise / Nouar, Dalila / Debray, Dominique / Lacaille, Florence / Picard, Capucine / Pérot, Philippe / Regnault, Béatrice / Da Rocha, Nicolas / de Cevins, Camille / Delage, Laure / Pérot, Brieuc P / Vinit, Angélique / Carbone, Francesco / Brunaud, Camille / Marchais, Manon / Stolzenberg, Marie-Claude / Asnafi, Vahid / Molina, Thierry / Rieux-Laucat, Frédéric / Notarangelo, Luigi D / Pittaluga, Stefania / Jais, Jean Philippe / Moshous, Despina / Blanche, Stephane / Malech, Harry / Eloit, Marc / Cavazzana, Marina / Fischer, Alain / Ménager, Mickaël M / Neven, Bénédicte

    The Journal of allergy and clinical immunology

    2023  Volume 151, Issue 6, Page(s) 1634–1645

    Abstract: 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 ... ...

    Abstract 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
    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.
    MeSH term(s) Humans ; Severe Combined Immunodeficiency/therapy ; Severe Combined Immunodeficiency/etiology ; CD8-Positive T-Lymphocytes ; Hematopoietic Stem Cell Transplantation/adverse effects ; Hematopoietic Stem Cell Transplantation/methods ; Virus Diseases/etiology ; Hepatitis/etiology ; Enterovirus Infections
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2022.12.822
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  7. Article ; Online: Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children.

    Avramescu, Marina / Isnard, Pierre / Temmam, Sarah / Chevalier, Agnès / Bastard, Paul / Attia, Mikael / Berthaud, Romain / Fila, Marc / Dossier, Claire / Hogan, Julien / Ulinski, Tim / Leguevaques, Damia / Louillet, Férielle / Casado, Edouard Martinez / Halimi, Jean-Michel / Cloarec, Sylvie / Zaloszyc, Ariane / Faudeux, Camille / Rousset-Rouvière, Caroline /
    Clavé, Stéphanie / Harambat, Jérôme / Rollot, Edouard / Simon, Thomas / Nallet-Amate, Megan / Ranchin, Bruno / Bacchetta, Justine / Porcheret, Florence / Bernard, Josselin / Ryckewaert, Amélie / Jamet, Anne / Fourgeaud, Jacques / Da Rocha, Nicolas / Pérot, Philippe / Kuperwasser, Nicolas / Bouazza, Naïm / Rabant, Marion / Duong Van Huyen, Jean-Paul / Robert, Matthieu P / Zuber, Julien / Casanova, Jean-Laurent / Eloit, Marc / Sermet-Gaudelus, Isabelle / Boyer, Olivia

    Kidney international

    2023  Volume 103, Issue 6, Page(s) 1193–1198

    MeSH term(s) Child ; Humans ; COVID-19/complications ; Nephritis, Interstitial/diagnosis ; Nephritis, Interstitial/drug therapy ; Post-Acute COVID-19 Syndrome ; Uveitis/diagnosis ; Uveitis/drug therapy ; Uveitis/etiology
    Language English
    Publishing date 2023-03-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 120573-0
    ISSN 1523-1755 ; 0085-2538
    ISSN (online) 1523-1755
    ISSN 0085-2538
    DOI 10.1016/j.kint.2023.02.028
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  8. Article ; Online: Acute tubulointerstitial nephritis with or without uveitis: a novel form of post-acute COVID-19 syndrome in children

    Avramescu, Marina / Isnard, Pierre / Temmam, Sarah / Chevalier, Agnes / Bastard, Paul / Attia, Mikael / Berthaud, Romain / Fila, Marc / Dossier, Claire / Hogan, Julien / Ulinski, Tim / Leguevaques, Damia / Louillet, Ferielle / Martinez Casado, Edouard / Halimi, Jean-Michel / Cloarec, Sylvie / Zaloszyc, Ariane / Faudeux, Camille / Rousset-Rouviere, Caroline /
    Clave, Stephanie / Harambat, Jerome / Rollot, Edouard / Simon, Thomas / Nallet-Amate, Megan / Ranchin, Bruno / Bacchetta, Justine / Porcheret, Florence / Bernard, Josselin / Ryckewaert, Amelie / Jamet, Anne / Fourgeaud, Jacques / Da Rocha, Nicolas / Perot, Philippe / Kuperwasser, Nicolas / Bouazza, Naim / Rabant, Marion / Duong Van Huyen, Jean-Paul / P Robert, Matthieu / Zuber, Julien / Casanova, Jean-Laurent / eloit, marc / Sermet-Gaudelus, Isabelle / Boyer, Olivia

    medRxiv

    Abstract: Background COVID-19 is a complex multisystem disease, frequently associated with kidney injury. Since the beginning of the COVID-19 pandemic, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with ... ...

    Abstract Background COVID-19 is a complex multisystem disease, frequently associated with kidney injury. Since the beginning of the COVID-19 pandemic, we observed a striking increase in the incidence of acute tubulointerstitial nephritis (aTIN) without or with uveitis (TINUs) among children. This prompted us to examine whether SARS-CoV-2 might be the underlying trigger. Methods We conducted a French nationwide retrospective cohort study. We included all consecutive children diagnosed with aTIN or TINUs of undetermined cause between April-2020 and March-2021. SARS-CoV-2 antibody responses were tested by a luciferase immunoprecipitation system and compared to age-matched controls. Immunohistochemistry, immunofluorescence and molecular microbiology analyses were performed on kidney biopsies. Results Forty-eight children were included with a median age at diagnosis of 14.7 years (9.4-17.6). aTIN and TINUs incidence rates increased 3-fold and 12-fold, respectively, compared to pre-pandemic years. All patients had impaired kidney function with a median eGFR of 31.9 ml/min/1.73m2 at diagnosis. Kidney biopsies showed lesions of acute tubulointerstitial nephritis and 25% of patients had fibrosis. No patient had concomitant acute COVID-19. All 16 children tested had high anti-N IgG titers and one had anti-S IgGs. Next-generation sequencing failed to detect any infectious agents in kidney biopsies. However, SARS-CoV-2 RNA was detected by PCR in two kidney samples supporting a potential direct link between SARS-CoV-2 and aTIN/TINUs. Conclusions We describe a novel form of post-acute COVID-19 syndrome in children, unique in its exclusive kidney and eye involvement, and its distinctive anti-SARS-CoV-2 N+/S- serological profile. Our results support a causal association linking SARS-CoV-2 infection to this newly-reported burst of renal/eye inflammation.
    Keywords covid19
    Language English
    Publishing date 2023-01-26
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.01.23.23284848
    Database COVID19

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