Long-Term Existence of SARS-CoV-2 in COVID-19 Patients: Host Immunity, Viral Virulence, and Transmissibility.
Long-Term Existence of SARS-CoV-2 in COVID-19 Patients: Host Immunity, Viral Virulence, and Transmissibility.
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SARS-CoV-2 在 COVID-19 患者中的长期存在：宿主免疫、病毒毒力和传播性
DOI：
10.1007/s12250-020-00308-0
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发表时间：
2020-12
影响因子：
5.5
通讯作者：
Xu S
中科院分区：
文献类型：
--
作者：
Wang X;Huang K;Jiang H;Hua L;Yu W;Ding D;Wang K;Li X;Zou Z;Jin M;Xu S
COVID-19患者可以在初始症状（PIS）后20天的中位SARS-CoV-2清除期内康复。然而，我们观察了一些患有SARS-CoV-2的COVID-19患者超过50天的PIS。本研究旨在探讨这些患者中病毒清除延迟的原因和感染性。收集了22名长期COVID-19患者的人口统计学数据和临床特征。研究队列的中位年龄为59.83 ± 12.94岁。所有患者均在长期SARS-CoV-2感染后（PIS 53 - 112天）临床治愈。外周淋巴细胞计数正常。IFN-γ分泌细胞占总CD 4+和CD 8+细胞的比例分别为24.68% ± 9.60%和66.41% ± 14.87%。但分泌IFN-γ的NK细胞数量减少（58.03% ± 11.78%）。所有患者均可检测到IgG，与轻度中和活性呈正相关（中和抗体滴度平均值= 157.2，P = 0.05）。所有患者PIS后50 d鼻咽拭子接种Vero E6细胞均未分离到SARS-CoV-2病毒，无细胞病变效应。但有1份样品在传代2代后细胞培养上清中SARS-CoV-2核酸检测呈阳性。基因组测序显示，只有三个同义变异的刺突蛋白编码区。结论：NK细胞产生IFN-γ的能力下降和中和抗体水平的降低可能有利于SARS-CoV-2的长期存在。此外，在长期SARS-CoV-2感染的COVID-19患者中观察到低病毒载量和弱病毒致病性。
COVID-19 patients can recover with a median SARS-CoV-2 clearance of 20 days post initial symptoms (PIS). However, we observed some COVID-19 patients with existing SARS-CoV-2 for more than 50 days PIS. This study aimed to investigate the cause of viral clearance delay and the infectivity in these patients. Demographic data and clinical characteristics of 22 long-term COVID-19 patients were collected. The median age of the studied cohort was 59.83 ± 12.94 years. All patients were clinically cured after long-term SARS-CoV-2 infection ranging from 53 to 112 days PIS. Peripheral lymphocytes counts were normal. The ratios of interferon gamma (IFN-γ)-secreting cells to total CD4+and CD8+cells were normal as 24.68% ± 9.60% and 66.41% ± 14.87% respectively. However, the number of IFN-γ-secreting NK cells diminished (58.03% ± 11.78%). All patients presented detectable IgG, which positively correlated with mild neutralizing activity (Mean value neutralisation antibodies titers = 157.2,P= 0.05). No SARS-CoV-2 virus was isolated in Vero E6 cells inoculated with nasopharyngeal swab samples from all patients 50 days PIS, and the cytopathic effect was lacking. But one sample was positive for SARS-CoV-2 nucleic acid test in cell supernatants after two passages. Genome sequencing revealed that only three synonymous variants were identified in spike protein coding regions. In conclusion, decreased IFN-γ production by NK cells and low neutralizing antibodies might favor SARS-CoV-2 long-term existence. Further, low viral load and weak viral pathogenicity were observed in COVID-19 patients with long-term SARS-CoV-2 infection.
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