Viruses in Vietnamese Patients Presenting with Community-Acquired Sepsis of Unknown Cause

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.

Keywords: Vietnam; community-acquired sepsis; viral metagenomics.

FIG 1

Flow chart showing an overview of the diagnostic output of the original study. *, see the original study (3) and Table S1 in the supplemental material for more details; ^#, the causative agents detected are detailed in the report of the original study (3); ^$, more details about the analysis of those 386 patients can be found in Fig. 2.

FIG 2

Flow chart showing how samples were analyzed. *, includes 4 pools of 5 samples, 3 pools of 4 samples, and 1 pool of 2 samples.

FIG 3

Bar chart showing the numbers of viruses known to be infectious to humans or previously reported in human tissues that were detected by mNGS, followed by PCR confirmation testing.

FIG 4

Numbers of viruses detected by mNGS, and then confirmed by virus-specific PCR, in clinical samples of different types.

FIG 5

Numbers of viruses detected by mNGS, and then confirmed by virus-specific PCR, in different patient groups and clinical entities. Symbols are color-coded by sample type. (A) All patients included in the mNGS analysis; (B) adults; (C) children.

FIG 5

Numbers of viruses detected by mNGS, and then confirmed by virus-specific PCR, in different patient groups and clinical entities. Symbols are color-coded by sample type. (A) All patients included in the mNGS analysis; (B) adults; (C) children.