• Aucun résultat trouvé

Human Coronavirus OC43 Associated with Fatal Encephalitis

N/A
N/A
Protected

Academic year: 2021

Partager "Human Coronavirus OC43 Associated with Fatal Encephalitis"

Copied!
2
0
0

Texte intégral

(1)

Correspondence

n engl j med 375;5 nejm.org August 4, 2016

Human Coronavirus OC43 Associated with Fatal Encephalitis

To the Editor: Encephalitis is a serious

neuro-logic syndrome characterized by brain inflam-mation that may be fatal. Although the majority of cases are caused by viruses, the identification of a causal organism can be difficult. Encepha-lopathy that affects patients with immunodefi-ciency is particularly challenging to diagnose, since the clinical presentation may be atypical and the differential diagnosis may include un-usual pathogens or a noninfective cause. Deep sequencing of clinical samples has the potential to identify the pathogens associated with en-cephalitis, particularly in cases in which tradi-tional techniques have not identified the candi-date causative pathogen.1

Here we report the use of deep sequencing of a brain biopsy sample obtained from an 11-month-old boy with severe combined immunodeficiency who had symptoms of viral encephalitis with negative results on conventional diagnostic poly-merase-chain-reaction (PCR) assay. The boy’s family provided written informed consent.

The boy underwent unconditioned cord-blood transplantation, which resulted in T-cell engraft-ment. Nonetheless, his condition continued to deteriorate, and he died 1.5 months after receiv-ing the transplant. RNA sequencreceiv-ing of a brain biopsy sample obtained 2 months after the onset of symptoms showed the presence of human coronavirus OC43 (HCoV-OC43), which was

sub-Figure 1. Immunohistochemical Analyses of Brain Tissue from an 11-Month-Old Boy with SCID and Symptoms of Viral Encephalitis.

Panel A shows prominent vacuolation with frequent karyorrhectic neurons (arrow) in the cerebral cortex (hema-toxylin and eosin) in an boy with severe combined immunodeficiency (SCID). A prominent microglial reaction was seen on CD68 immunohistochemical staining (Panel B), along with multiple collections of infiltrating T cells (Panel C). The nucleocapsid protein of human coronavirus OC43 showed positive staining in the neurons and neuropil (Panel D).

A

20 µm 100 µm

100 µm 50 µm

C D

B

The New England Journal of Medicine

Downloaded from nejm.org on August 24, 2016. For personal use only. No other uses without permission. Copyright © 2016 Massachusetts Medical Society. All rights reserved.

(2)

correction

n engl j med 375;5 nejm.org August 4, 2016

sequently confirmed on real-time PCR (thresh-old cycle, 24) and brain immunohistochemical analysis (Fig. 1). Full details on the case history, library preparation, bioinformatics analysis, spe-cies identification as reported by the profiling method metaMix,2 PCR confirmation,

immuno-histochemical analysis, and phylogenetic and variant analyses are provided in the Supplemen-tary Appendix, available with the full text of this letter at NEJM.org.

The human betacoronaviruses, including HCoV-OC43, are predominantly associated with respiratory tract infections. The group includes viruses that cause the severe acute respiratory syndrome and the Middle East respiratory syn-drome. HCoV-OC43 is generally associated with mild upper respiratory tract infections, although it has been shown to have neuroinvasive proper-ties. In vivo studies in mice have shown that HCoV-OC43 can infect neurons and cause en-cephalitis.3 The virus has also been shown to

cause persistent infections in human neural-cell lines.4 A single report identified HCoV-OC43

RNA in the cerebrospinal fluid of a child with acute disseminated encephalomyelitis.5 In the case

we describe here, three independent methods were used to identify HCoV-OC43 in brain tissue of a child with acute encephalomyelitis.

Deep sequencing of biopsy material provides an important tool for the diagnosis of unex-plained encephalomyelitis, particularly in patients with immunodeficiency who have undergone stem-cell transplantation, when the differential diagnosis may include immune-mediated inflam-mation or drug toxicity. The identification of a pathogen can provide important support for treatment decisions, such as changes in the im-munosuppression regimen or the use of specific treatments. Standardization of protocols and analyses will aid in the development of this ap-proach for the treatment of such patients. Sofia Morfopoulou, Ph.D.

University College London London, United Kingdom sofia.morfopoulou.10@ucl.ac.uk

Julianne R. Brown, M.Sc.

E. Graham Davies, M.B., F.R.C.P.C.H. Glenn Anderson, F.I.B.M.S.

Alex Virasami, M.Res.

Great Ormond Street Hospital for Children NHS Foundation Trust London, United Kingdom

Waseem Qasim, M.B., B.S., Ph.D.

University College London London, United Kingdom

Wui K. Chong, M.D.

Great Ormond Street Hospital for Children NHS Foundation Trust

London, United Kingdom

Michael Hubank, Ph.D. Vincent Plagnol, Ph.D.

University College London London, United Kingdom

Marc Desforges, Ph.D.

INRS-Institut Armand-Frappier Laval, QC, Canada

Thomas S. Jacques, Ph.D.

University College London London, United Kingdom

Pierre J. Talbot, Ph.D.

INRS-Institut Armand-Frappier Laval, QC, Canada

Judith Breuer, M.D.

University College London London, United Kingdom

Supported by the UCL National Institute for Health Research Biomedical Research Centres at University College London Hos-pitals and Great Ormond Street Hospital for Children NHS Foundation Trust.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

1. Brown JR, Morfopoulou S, Hubb J, et al. Astrovirus VA1/ HMO-C: an increasingly recognized neurotropic pathogen in immunocompromised patients. Clin Infect Dis 2015; 60: 881-8.

2. Morfopoulou S, Plagnol V. Bayesian mixture analysis for meta-genomic community profiling. Bioinformatics 2015; 31: 2930-8.

3. Talbot PJ, Desforges M, Brison E, Jacomy H. Coronaviruses as encephalitis-inducing infectious agents. In: Tkachev S, ed. Non-flavivirus encephalitis. Rijeka, Croatia: InTech, 2011: 185-202.

4. Arbour N, Côté G, Lachance C, Tardieu M, Cashman NR, Talbot PJ. Acute and persistent infection of human neural cell lines by human coronavirus OC43. J Virol 1999; 73: 3338-50.

5. Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics 2004; 113(1 Pt 1): e73-6.

DOI: 10.1056/NEJMc1509458

Correspondence Copyright © 2016 Massachusetts Medical Society.

correction

Zika and the Risk of Microcephaly (July 7, 2016;375:1-4). In Figure 1 (page 2), the second-trimester and third-trimester graphs (Panels D and F) were transposed. The article is correct at NEJM.org.

The New England Journal of Medicine

Downloaded from nejm.org on August 24, 2016. For personal use only. No other uses without permission. Copyright © 2016 Massachusetts Medical Society. All rights reserved.

Figure

Figure 1.  Immunohistochemical Analyses of Brain Tissue from an 11-Month-Old Boy with SCID and Symptoms  of Viral Encephalitis.

Références

Documents relatifs

Mais, en fait, le point fixe (ou en mouvement uniforme) est le centre de masse du système et il est alors naturel d’imaginer les deux corps en rotation autour du centre de

Thali MJ, Yen K, Schweitzer W, Vock P, Boesch C, Ozdoba C, Schroth G, Ith M, Sonnenschein M, Doernhofer T, Scheurer E, Plattner T, Dirnhofer R (2003) Virtopsy, a new imaging horizon

Une construction naturelle est également celle constituée autour d’un terme générique avec le syntagme DNI dans une position adverbiale, cette fois plutôt juste avant

Effet de la temperature des racines sur leur respiration et sur la croissance des plantules de deux hybrides de maïs... Effet de la température des racines sur leur

Overell J, Hsieh S, Odaka M, Yuki N, Willison H: Treatment for Fisher syndrome, Bickerstaff ’s brainstem encephalitis and related disorders.. Cochrane Database Syst Rev 2007,

Nous montrons, comme dans le chapitre 2, que le d´etecteur MAP utilisant l’estimateur bootstrap du canal peut ˆetre approxim´e par un d´etecteur MAP connaissant parfaitement le

The JPL ephemerides DE432 + URA111 were used in all computations: construction of ephemeris curves for distance and relative velocity, pixel scale, orientation angle, (α,

Abdou Bontianti, Catherine Baron et Alain Bonnassieux, 2012 : « Revue de la littérature sur la pauvreté, l’eau, l’assainissement au Niger et la gouvernance urbaine à Niamey »