Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series.
Daily Viral Kinetics and Innate and Adaptive Immune Response Assessment in COVID-19: a Case Series.
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DOI：
10.1128/msphere.00827-20
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发表时间：
2020-11-11
期刊：
影响因子：
4.8
通讯作者：
Eckerle I
中科院分区：
文献类型：
--
作者：
Vetter P;Eberhardt CS;Meyer B;Martinez Murillo PA;Torriani G;Pigny F;Lemeille S;Cordey S;Laubscher F;Vu DL;Calame A;Schibler M;Jacquerioz F;Blanchard-Rohner G;Siegrist CA;Kaiser L;Didierlaurent AM;Eckerle I
这项工作特别重要，因为它同时评估了相同受试者的病毒学，免疫学和临床表现，而其他研究分别评估这些。我们描述了在瑞士日内瓦被隔离的前五名SARS-CoV-2感染患者的详细病毒和免疫特征。病毒载量在疾病开始时达到峰值，传染性病毒仅在疾病的早期急性期脱落。在症状发作后7天，通过培养不能分离出感染性病毒，而病毒RNA在很长一段时间内仍可检测到。重要的是，我们看到所有患者，即使是那些症状轻微的患者，都能产生足以控制病毒的先天性反应（以早期激活的细胞因子和单核细胞反应为特征），并产生特异性免疫以及细胞和体液SARS-CoV-2特异性适应性反应，这些反应在症状消退后开始下降。在2019年轻度冠状病毒病（COVID-19）中，病毒脱落模式及其与免疫反应的相关性仍然很差。我们监测了在瑞士日内瓦隔离的前五名患者的病毒RNA和传染性病毒的脱落，并表征了其免疫应答动力学。尽管症状轻微，但仍观察到呼吸道的高病毒载量和感染性病毒脱落，并通过逆转录酶PCR（RT-PCR）分离出感染性病毒并延长阳性时间，分别直至症状发作后第7天和第19天。早在症状发作后2天就观察到以活化的CD 14 + CD 16+单核细胞和细胞因子应答增加为特征的稳健的先天性应答。细胞和体液严重急性呼吸综合征（SARS）-CoV-2特异性适应性反应在所有患者中均可检测到。感染性病毒脱落仅限于症状发作后的第一周。一个强大的先天性反应，其特征是动员活化的单核细胞在感染的第一天和SARS-CoV-2特异性抗体，是检测即使在轻度疾病的患者。这项工作特别重要，因为它同时评估了相同受试者的病毒学，免疫学和临床表现，而其他研究分别评估这些。我们描述了在瑞士日内瓦被隔离的前五名SARS-CoV-2感染患者的详细病毒和免疫特征。病毒载量在疾病开始时达到峰值，传染性病毒仅在疾病的早期急性期脱落。在症状发作后7天，通过培养不能分离出感染性病毒，而病毒RNA在很长一段时间内仍可检测到。重要的是，我们看到所有患者，即使是那些症状轻微的患者，都能产生足以控制病毒的先天性反应（以早期激活的细胞因子和单核细胞反应为特征），并产生特异性免疫以及细胞和体液SARS-CoV-2特异性适应性反应，这些反应在症状消退后开始下降。
This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms. Viral shedding patterns and their correlations with immune responses are still poorly characterized in mild coronavirus (CoV) disease 2019 (COVID-19). We monitored shedding of viral RNA and infectious virus and characterized the immune response kinetics of the first five patients quarantined in Geneva, Switzerland. High viral loads and infectious virus shedding were observed from the respiratory tract despite mild symptoms, with isolation of infectious virus and prolonged positivity by reverse transcriptase PCR (RT-PCR) until days 7 and 19 after symptom onset, respectively. Robust innate responses characterized by increases in activated CD14+ CD16+ monocytes and cytokine responses were observed as early as 2 days after symptom onset. Cellular and humoral severe acute respiratory syndrome (SARS)-CoV-2-specific adaptive responses were detectable in all patients. Infectious virus shedding was limited to the first week after symptom onset. A strong innate response, characterized by mobilization of activated monocytes during the first days of infection and SARS-CoV-2-specific antibodies, was detectable even in patients with mild disease. IMPORTANCE This work is particularly important because it simultaneously assessed the virology, immunology, and clinical presentation of the same subjects, whereas other studies assess these separately. We describe the detailed viral and immune profiles of the first five patients infected by SARS-CoV-2 and quarantined in Geneva, Switzerland. Viral loads peaked at the very beginning of the disease, and infectious virus was shed only during the early acute phase of disease. No infectious virus could be isolated by culture 7 days after onset of symptoms, while viral RNA was still detectable for a prolonged period. Importantly, we saw that all patients, even those with mild symptoms, mount an innate response sufficient for viral control (characterized by early activated cytokines and monocyte responses) and develop specific immunity as well as cellular and humoral SARS-CoV-2-specific adaptive responses, which already begin to decline a few months after the resolution of symptoms.