Data_Sheet_1_The Identification and Genetic Characterization of Parechovirus Infection Among Pediatric Patients With Wide Clinical Spectrum in Chongqing, China.docx

Human parechoviruses (HPeVs) are important causes of infection in children. However, without a comprehensive and persistent surveillance, the epidemiology and clinical features of HPeV infection remain ambiguous. We performed a hospital-based surveillance study among three groups of pediatric patients with acute respiratory infection (Group 1), acute diarrhea (Group 2), and hand, foot and mouth disease (Group 3) in Chongqing, China, from 2009 to 2015. Among 10,212 tested patients, 707 (6.92%) were positive for HPeV, with the positive rates differing significantly among three groups (Group 1, 3.43%; Group 2, 14.94%; Group 3, 3.55%; P < 0.001). The co-infection with other pathogens was detected in 75.2% (531/707) of HPeV-positive patients. Significant negative interaction between HPeV and Parainfluenza virus (PIV) (P = 0.046, OR = 0.59, 95% CI = 0.34–0.98) and positive interactions between HPeV and Enterovirus (EV) (P = 0.015, OR = 2.28, 95% CI = 1.23–4.73) were identified. Among 707 HPeV-positive patients, 592 (83.73%) were successfully sequenced, and 10 genotypes were identified, with HPeV1 (n = 396), HPeV4 (n = 86), and HPeV3 (n = 46) as the most frequently seen. The proportion of genotypes differed among three groups (P < 0.001), with HPeV1 and HPeV4 overrepresented in Group 2 and HPeV6 overrepresented in Group 3. The spatial patterns of HPeV genotypes disclosed more close clustering of the currently sequenced strains than those from other countries/regions, although they were indeed mixed. Three main genotypes (HPeV1, HPeV3, and HPeV4) had shown distinct seasonal peaks, highlighting a bi-annual cycle of all HpeV and two genotypes (HPeV 1 and HPeV 4) with peaks in odd-numbered years and with peaks in even-numbered years HPeV3. Significantly higher HPeV1 viral loads were associated with severe diarrhea in Group 2 (P = 0.044), while associated with HPeV single infection than HPeV-EV coinfection among HFMD patients (P = 0.001). It’s concluded that HPeV infection was correlated with wide clinical spectrum in pediatric patients with a high variety of genotypes determined. Still no clinical significance can be confirmed, which warranted more molecular surveillance in the future.

人源 parechovirus（HPeVs）是儿童感染的重要病原体。然而，由于缺乏全面且持续的监测，HPeV感染的流行病学特征及临床特点仍然模糊不清。本研究在重庆市于2009至2015年间对急性呼吸道感染（第1组）、急性腹泻（第2组）以及手足口病（第3组）的三组儿科患者进行了基于医院的监测研究。在10,212名接受检测的患者中，707名（6.92%）检测出HPeV阳性，三个组的阳性率存在显著差异（第1组，3.43%；第2组，14.94%；第3组，3.55%；P < 0.001）。在707名HPeV阳性患者中，有75.2%（531名）检测到与其他病原体的共感染。HPeV与副流感病毒（PIV）之间存在显著的负相关性（P = 0.046，OR = 0.59，95% CI = 0.34–0.98），与肠道病毒（EV）之间存在阳性相互作用（P = 0.015，OR = 2.28，95% CI = 1.23–4.73）。在707名HPeV阳性患者中，有592名（83.73%）成功进行了测序，共鉴定出10个基因型，其中HPeV1（n = 396）、HPeV4（n = 86）和HPeV3（n = 46）最为常见。三个组的基因型比例存在差异（P < 0.001），在第2组中HPeV1和HPeV4基因型占比过高，而在第3组中HPeV6基因型占比过高。HPeV基因型的空间分布模式显示，目前测序的菌株与其他国家/地区的菌株相比，表现出更紧密的集群，尽管它们确实存在混合。三种主要基因型（HPeV1、HPeV3和HPeV4）显示出明显的季节性高峰，突显了所有HPeV以及基因型HPeV 1和HPeV 4的年度周期，其中HPeV 1和HPeV 4在奇数年达到高峰，而HPeV3在偶数年达到高峰。在第2组中，显著更高的HPeV1病毒载量与严重的腹泻相关（P = 0.044），而在手足口病患者中，与HPeV单感染相比，与HPeV-EV共感染相关（P = 0.001）。结论表明，HPeV感染与儿科患者广泛的临床谱相关，且由多种基因型确定。然而，至今尚无临床意义得到确认，这要求未来进行更多的分子监测。