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. 2019 Aug 29;10(9):661.
doi: 10.3390/genes10090661.

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

Verena Kufner  1 , Andreas Plate  2 , Stefan Schmutz  1 , Dominique L Braun  1   2 , Huldrych F Günthard  1   2 , Riccarda Capaul  1 , Andrea Zbinden  1 , Nicolas J Mueller  3 , Alexandra Trkola  4 , Michael Huber  5
Affiliations

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

Verena Kufner et al. Genes (Basel). .

Abstract

Metagenomic next-generation sequencing (mNGS) can capture the full spectrum of viral pathogens in a specimen and has the potential to become an all-in-one solution for virus diagnostics. To date, clinical application is still in an early phase and limitations remain. Here, we evaluated the impact of viral mNGS for cases analyzed over two years in a tertiary diagnostics unit. High throughput mNGS was performed upon request by the treating clinician in cases where the etiology of infection remained unknown or the initial differential diagnosis was very broad. The results were compared to conventional routine testing regarding outcome and workload. In total, 163 specimens from 105 patients were sequenced. The main sample types were cerebrospinal fluid (34%), blood (33%) and throat swabs (10%). In the majority of the cases, viral encephalitis/meningitis or respiratory infection was suspected. In parallel, conventional virus diagnostic tests were performed (mean 18.5 individually probed targets/patients). mNGS detected viruses in 34 cases (32%). While often confirmatory, in multiple cases, the identified viruses were not included in the selected routine diagnostic tests. Two years of mNGS in a tertiary diagnostics unit demonstrated the advantages of a single, untargeted approach for comprehensive, rapid and efficient virus diagnostics, confirming the utility of mNGS in complementing current routine tests.

Keywords: clinical impact; diagnostics; metagenomic sequencing; virus; virus infection.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Case statistics of samples analyzed by viral metagenomic next-generation sequencing (mNGS). (A) Sample types analyzed in 105 cases over two years shown in percentage. Swab (other) includes enoral swab, skin swab, nasopharyngeal secretion and unknown swab. Others includes DNA extract of myocardial biopsy, sonicate of a knee implant and cell culture supernatant. (B) Number of samples and sample types analyzed per department. Others includes otorhinolaryngology, dermatology, rheumatology and external sources. BAL: Broncho-alveolar lavage, CSF: Cerebrospinal fluid. Bar labels indicate the total count.
Figure 2
Figure 2
Viruses reported by viral mNGS. Krona chart of detected and reported viruses on family and species level with DNA viruses shown in green and RNA viruses shown in red. Reference krona chart: [31].
Figure 3
Figure 3
Timing of viral mNGS: (A) the delay (in days) between the time point when the clinical specimen was collected and the metagenomic test was requested; and (B) the delay (in days) between metagenomic test request and validation, corresponding to reporting of the results to the physician.
Figure 3
Figure 3
Timing of viral mNGS: (A) the delay (in days) between the time point when the clinical specimen was collected and the metagenomic test was requested; and (B) the delay (in days) between metagenomic test request and validation, corresponding to reporting of the results to the physician.
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