背景:在患者住院期间,病毒脱落的动力学和针对猴痘病毒(MPXV)的特异性体液反应尚未得到很好的表征。这项研究的目的是使用来自住院患者的纵向配对收集的样本来确定病毒载量和针对MPXV的抗体水平。
方法:于2023年6月2日至9月23日在中国首都医科大学附属北京地坛医院招募了因痘住院的患者。配对样品,包括皮肤损伤的样本,口咽,唾液,粪便,尿液,等离子体,和血清,在入院后第1、3、7和14天连续收集,直至出院。并非所有患者都具有在所有时间点获得的样品。通过定量PCR分析所有样品。通过使用临床样品和Vero细胞进行病毒分离。IgM的存在,IgA,IgG,并评估了针对MPXV的中和抗体(NAb)。第一次采集的血浆样本是在患者住院时采集的,并测量样品中细胞因子和趋化因子的水平。人口统计数据,天花疫苗接种状况,已知接触MPVX的历史,使用标准病例报告表收集HIV状况和其他临床数据。
结果:从39名被招募的水痘患者中连续采集了510个标本。在所有样本中,皮损的病毒DNA检出率和病毒载量最高,唾液样本的比率和病毒载量位居第二。出院前一天,85%的干屑(Ct中位数28.2,范围19.0-38.3)和70%的唾液样本(Ct中位数32.4,范围24.5-38.1)对病毒DNA呈阳性,其中,在病毒培养中,有23.1%的干草呈阳性。口咽中病毒DNA的检出率,唾液,粪便样本随时间减少,而血浆中的速率,血清,尿样在症状发作(PSO)后10天之前迅速增加。MPXV-IgM出现的中位天数,MPXV-IgA,MPXV-IgG,NAb在8(四分位数间距[IQR]7-9),9(7-10)12(9-15)和12(9-15)PSO,分别。IgM,IgA,IgG,NAb滴度随时间增加。在第11天和第21天之间,PSO,HIV感染者(PWH)的NAb滴度低于无HIV感染者(PWOH).NAb滴度增加与唾液中病毒载量降低相关(r=0.28,p=0.025),粪便(r=0.35,p=0.021),血浆(r=0.30,p=0.0044),和血清样本(r=0.37,p=0.001)。与PWOH相比,PWH有较高的血浆MIP-1α水平,MIP-1β,G-CSF,IL-4和碱性FGF。
结论:患者出院时,临床样本的病毒培养阳性率较高,这表明对患水痘的人需要有效的公共卫生管理策略。PWH中的低NAb滴度和高水平的细胞因子表明,需要早期治疗来控制高危人群的炎症。
背景:国家自然科学基金,中国医学科学院,北京协和医学院中央大学基础研究基金,国家重点研发计划.
BACKGROUND: The dynamics of viral shedding and the specific humoral response against monkeypox virus (MPXV) have not been well characterized in patients across their disease course during hospitalisation. The aim of this study was to determine the viral load and the levels of antibodies against MPXV using longitudinal paired-collected samples from hospitalized patients.
METHODS: Patients who were hospitalised with mpox were recruited at Beijing Ditan Hospital Capital Medical University in
China between June 2 and September 23, 2023. Paired samples, including samples from skin lesions, the oropharynx, saliva, faeces, urine, plasma, and serum, were serially collected at days 1, 3, 7, and 14 after admission until discharge. Not all of the patients had samples obtained at all of the timepoints. All the samples were analysed via quantitative PCR. Virus isolation was performed by using clinical samples and Vero cells. The presence of IgM, IgA, IgG, and neutralising antibodies (NAbs) against MPXV was evaluated. The first collected plasma sample was taken when the patient was hospitalised, and the levels of cytokines and chemokines were measured in the sample. The demographic data, smallpox vaccination status, history of known exposure to MPVX, HIV status and other clinical data were collected using a standard case report form.
RESULTS: A total of 510 specimens were serially collected from 39 recruited people with mpox. Among all the samples, the skin lesions had the highest viral DNA detection rates and viral loads, and the saliva samples had the second highest rates and viral loads. One day before discharge, 85% of the dry scrabs (median Ct 28.2, range 19.0-38.3) and 70% of the saliva samples (median Ct 32.4, range 24.5-38.1) were positive for viral DNA, Of which, 23.1% of dry scrabs were positive in viral culture. The rate of viral DNA detection in the oropharyngeal, saliva, and faecal samples decreased with time, while the rates in the plasma, serum, and urine samples increased quickly before 10 days post symptom onset (PSO). The median days of appearance of MPXV-IgM, MPXV-IgA, MPXV-IgG, and NAb were at 8 (interquartile range [IQR] 7-9), 9 (7-10), 12 (9-15), and 12 (9-15) PSO, respectively. The IgM, IgA, IgG, and NAb titres increased with time. Between days 11 and 21 PSO, the NAb titres were lower in people living with HIV (PWH) than in people living without HIV (PWOH). Increased NAb titres were associated with decreased viral loads in the saliva (r = 0.28, p = 0.025), faeces (r = 0.35, p = 0.021), plasma (r = 0.30, p = 0.0044), and serum samples (r = 0.37, p = 0.001). Compared with PWOH, PWH had higher plasma levels of MIP-1α, MIP-1β, G-CSF, IL-4, and FGF-basic.
CONCLUSIONS: The high positive viral culture rate of clinical samples of patients when they are discharged from the hospital indicates that effective public health management strategies are needed for people with mpox. The low NAb titres and high levels of cytokines in PWH shows that earlier treatment is needed to control inflammation in high-risk populations.
BACKGROUND: National Natural Science Foundation of
China, Chinese Academy of Medical Sciences, Fundamental Research Funds for the Central Universities for Peking Union Medical College, National Key R&D Program of
China.