Persistent mammalian orthoreovirus, coxsackievirus and adenovirus co-infection in a child with a primary immunodeficiency detected by metagenomic sequencing: a case report

Abstract

BackgroundWe report a rare case of Mammalian orthoreovirus (MRV) infection in a child with a primary immunodeficiency (PID). Infections with Mammalian orthoreovirus are very rare and probably of zoonotic origin. Only a few cases have been described so far, including one with similar pathogenesis as in our case.Case presentationThe patient, age 11, presented with flu-like symptoms and persistent severe diarrhea. Enterovirus has been detected over several months, however, exact typing of a positive cell culture remained inconclusive. Unbiased metagenomic sequencing then detected MRV in stool samples from several time points. The sequencing approach further revealed co-infection with a recombinant Coxsackievirus and Adenovirus. MRV-specific antibodies detected by immunofluorescence proved that the patient seroconverted.ConclusionThis case highlights the potential of unbiased metagenomic sequencing in supplementing routine diagnostic methods, especially in situations of chronic infection with multiple viruses as seen here in an immunocompromised host. The origin, transmission routes and implications of MRV infection in humans merit further investigation.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-2946-7) contains supplementary material, which is available to authorized users.

Two Years of Viral Metagenomics in a Tertiary Diagnostics Unit: Evaluation of the First 105 Cases

“…Clinical samples were pre-processed upon arrival and nucleic acid extracts were collected and batched for weekly sequencing runs. mNGS and data analysis were performed as described previously in a subset of patients ( n = 11, protocol v1.0.0, [26,28]). The remaining patients ( n = 94) were analyzed using an adapted metagenomic workflow, which was established during the past years ().…”

“…In 2017, we introduced virus sequence-independent metagenomic high-throughput sequencing at our tertiary diagnostic unit and established protocols for sample preparation, sequencing and bioinformatics analysis [26]. This analysis workflow has proven highly successful enabling us to detect disease causing viral pathogens in complex clinical cases [27,28,29]. Since 2017, viral mNGS was applied in 105 primarily hard-to-diagnose cases upon request by the treating clinician.…”

Enteric Viral Co-Infections: Pathogenesis and Perspective

“…An investigation in HIV-seropositive and -seronegative children with diarrhea in Brazil reported a significantly higher rate of co-infections with >1 enteric virus including NoV, AdV and human bocavirus in HIV-1 seropositive children [110]. There have also been a number of case reports of severe co-infections in immunocompromised individuals, such as those of AdV and coxsackievirus detected in a child with a primary immunodeficiency with persistent severe diarrhea [111], or AdV and NoV co-infection reported in a patient diagnosed with chronic myeloid leukemia undergoing stem cell transplantation [112]. Certainly, immunocompromised patients with AGE are at increased risk of complications and prolonged hospitalizations.…”

Metagenomic Virome Sequencing in Living Donor and Recipient Kidney Transplant Pairs Revealed JC Polyomavirus Transmission

“…Metagenomic sequencing and data analysis was performed as described previously [15,16] (Supplementary Methods). Briefly, samples were centrifuged, filtered (0.45 μm), and nuclease-treated.…”