Real-time Utilization of Metagenomic Sequencing in the Diagnosis and Treatment Monitoring of an Invasive Adenovirus B55 Infection and Subsequent Herpes Simplex Virus Encephalitis in an Immunocompetent Young Adult

Abstract

BackgroundMetagenomic sequencing has shown tremendous promise in solving difficult infectious diseases cases. In this study, we utilized this technology to help guide the care of a critically ill patient with severe pneumonia, fever of unknown origin, and subsequent encephalitis in the intensive care unit (ICU).MethodsShotgun metagenomic sequencing was performed on the patient’s blood, bronchoalveolar lavage (BAL), and cerebral spinal fluid by using an Illumina MiniSeq sequencer.Results. A high load of human adenovirus B55 (HAdV-B55), a highly pathogenic adenovirus associated with numerous recently reported outbreaks and deaths in China, was detected in both blood and BAL, which explained the severity of the condition. The patient was treated with intravenous ribavirin, which cleared the virus after 26 days. Metagenomic sequencing also helped diagnose an unexpected herpes simplex virus–1 encephalitis during hospitalization, which led to timely treatment.Conclusions. This was the first successful case utilizing metagenomic sequencing to guide diagnosis and treatment in the ICU setting in China. We have proven the concept that metagenomic sequencing can play an important role in determining clinical approaches and ultimately in improving patient outcomes. We also hope to share our successful treatment protocol for the severe pneumonia and viremia caused by HAdV-B55.

Perspective on Adenoviruses: Epidemiology, Pathogenicity, and Gene Therapy

“…Of these, only some cause severe infections, leading to meningitis, conjunctivitis, gastroenteritis, and/or acute hemorrhagic cystitis [6,8,9,10,11]. Most of these infections occur in children [12,13], the elderly [14,15], and people with a severely compromised immune system [7,16,17]. The association of HAdV serotypes with a specific disease, however, has not been fully elucidated, as the clinical manifestations are sometimes linked to the site of viral inoculation [8,18].…”

Community acquired Stenotrophomonas maltophilia discitis: Diagnosis aided by shotgun metagenomic sequencing

“…We performed a laboratory developed PCR test targeting the smeT gene specific to S. maltophilia, which was positive in the spinal tissues, thus confirming the results of the metagenomic sequencing (supplemental Figure S2). Our case report adds to a growing body of literature illustrating the value of metagenomic sequencing for pathogen detection (Fang et al, 2018;Thoendel et al, 2018) and highlights its utility in cases of culture-negative infections, especially when patients have been empirically treated for a prolonged period of time. To the best of our knowledge, this is the first case report of community acquired discitis and epidural abscess associated with dry cupping therapy in an immunocompetent child.…”

Case Report: Epstein–Barr Virus Encephalitis Complicated With Brain Stem Hemorrhage in an Immune-Competent Adult

“…Additionally, pathogen detection in the CSF was performed by NGS. The NGS detection method was the same as we described before (22). The measured CSF pressure was 310 mm H 2 O, and the CSF was still colorless and not turbid.…”