Abstract
Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for >50% of the patients. Here we applied metagenomic next-generation sequencing (mNGS) to characterize the human virome in 492 clinical samples (384 sera, 92 pooled nasal and throat swabs, 10 stools, and 6 cerebrospinal fluid samples) from 386 patients (213 adults and 173 children) presenting with CA sepsis who were recruited from 6 hospitals across Vietnam between 2013 and 2015. Specific monoplex PCRs were used subsequently to confirm the presence of viral sequences detected by mNGS. We found sequences related to 47 viral species belonging to 21 families in 358 of 386 (93%) patients, including viruses known to cause human infections. After PCR confirmation, human viruses were found in 52 of 386 patients (13.4%); picornavirus (enteroviruses [n = 14], rhinovirus [n = 5], and parechovirus [n = 2]), hepatitis B virus (n = 10), cytomegalovirus (n = 9), Epstein-Barr virus (n = 5), and rotavirus A (n = 3) were the most common viruses detected. Recently discovered viruses were also found (gemycircularvirus [n = 5] and WU polyomavirus, Saffold virus, salivirus, cyclovirus-VN, and human pegivirus 2 [HPgV2] [n, 1 each]), adding to the growing literature about the geographic distribution of these novel viruses. Notably, sequences related to numerous viruses not previously reported in human tissues were also detected. To summarize, we identified 21 viral species known to be infectious to humans in 52 of 386 (13.4%) patients presenting with CA sepsis of unknown cause. The study, however, cannot directly impute sepsis causation to the viruses identified. The results highlight the fact that it remains a challenge to establish the causative agents in CA sepsis patients, especially in tropical settings such as Vietnam.
Highlights
Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for Ͼ50% of the patients
Among the 386 patients with sepsis of unknown cause whose data were included in the metagenomic next-generation sequencing (mNGS) analysis, the most frequent clinical entity was acute respiratory infection (n ϭ 158 [41%]), followed by systemic infection (n ϭ 152 [39.5%]), diarrhea (n ϭ 36 [9.3%]), and central nervous system (CNS) infection (n ϭ 40 [10.5%]) (Table 1) [3]
nucleic acid (NA) sequences of 21 viral species known to be infectious to humans were detected in 137 of 466 (29%) clinical samples from 125 of 386 (32%) individuals by viral metagenomics
Summary
Community-acquired (CA) sepsis is a major public health problem worldwide, yet the etiology remains unknown for Ͼ50% of the patients. We identified 21 viral species known to be infectious to humans in 52 of 386 (13.4%) patients presenting with CA sepsis of unknown cause. In. a recent etiological study of 1,578 patients with CA sepsis, conducted by the Southeast Asia Infectious Disease Clinical Research Network, the etiology (viruses, bacteria, and parasites) was established for only 48% [3]. A recent etiological study of 1,578 patients with CA sepsis, conducted by the Southeast Asia Infectious Disease Clinical Research Network, the etiology (viruses, bacteria, and parasites) was established for only 48% [3] While this diagnostic yield is comparable to that of previous reports, the unknown etiology for Ͼ50% of the patients may be attributed to the low sensitivity of current diagnostic tests and/or the diversity of the causative agents that may be responsible for this important clinical condition. We use mNGS to characterize the viral contents of clinical samples collected from patients enrolled in an etiological study of sepsis of unknown etiology across Southeast Asia between 2013 and 2015 [3]
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