Direct Evidence of Active SARS-CoV-2 Replication in the Intestine
Direct Evidence of Active SARS-CoV-2 Replication in the Intestine
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DOI：
10.1093/cid/ciaa925
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发表时间：
2021-08-01
影响因子：
11.8
通讯作者：
Jiang, Congqing
中科院分区：
文献类型：
--
作者：
Qian, Qun;Fan, Lifang;Jiang, Congqing
背景目前，尚无直接证据证明严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）在肠道内的活跃复制和结肠、直肠的相关病理改变。我们研究了临床确诊的2019冠状病毒病（COVID-19）伴直肠腺癌患者的手术直肠组织中病毒体和病理变化的存在。在该患者住院和随访期间收集临床数据。对手术切除的直肠组织、回肠造口的肠液和肠粘膜以及恢复后随访的直肠粘膜进行定量逆转录-聚合酶链反应（RT-PCR）。用电子显微镜观察超薄切片的手术样本中的SARS-CoV-2病毒粒子。采用苏木精-伊红染色进行组织学检查。采用免疫组化和免疫荧光法检测直肠组织SARS-CoV-2抗原的分布和免疫细胞浸润情况。患者于术后第3天出现发热和咳嗽，于第7天被诊断为COVID-19，并于第41天出院。在手术切除的直肠标本中检测到SARS-CoV-2的RNA，但在出院后37天收集的样本中未检测到。值得注意的是，与SARS-CoV-2核酸检测呈阳性的手术标本直肠组织相一致，电子显微镜下观察到直肠组织中存在典型的冠状病毒病毒粒子。此外，还发现大量淋巴细胞和巨噬细胞（部分SARS-CoV-2阳性）浸润固有层，但黏膜无明显损伤。我们首先报告了在潜伏期内SARS-CoV-2在患者直肠中活跃复制的直接证据，这可能解释SARS-CoV-2粪-口传播。
Background. Currently, there is no direct evidence to prove the active replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the intestinal tract and relevant pathological changes in the colon and rectum. We investigated the presence of virions and pathological changes in surgical rectal tissues of a patient with clinically confirmed coronavirus disease 2019 (COVID-19) with rectal adenocarcinoma.Methods. The clinical data were collected during hospitalization and follow-up of this patient. Quantitative reverse transcriptase-polymerasechain reaction (RT-PCR) was performed on the rectal tissue specimens obtained from surgical resection, succus entericus and intestinal mucosa of ileostomy, and rectal mucosa during follow-up after recovery. Ultrathin sections of surgical samples were observed for SARS-CoV-2 virions using electron microscopy. Histopathological examination was performed using hematoxylin-eosin stain. Immunohistochemical analysis and immunofluorescence were carried out on rectal tissues to evaluate the distribution of SARS-CoV-2 antigen and immune cell infiltrations.Results. The patient had fever and cough on day 3 postoperatively, was diagnosed with COVID-19 on day 7, and was discharged from the hospital on day 41. RNA of SARS-CoV-2 was detected in surgically resected rectal specimens but not in samples collected 37 days after discharge. Notably, coincident with rectal tissues of surgical specimens testing nucleic acid positive for SARS-CoV-2, typical coronavirus virions in rectal tissue were observed under electron microscopy. Moreover, abundant lymphocytes and macrophages (some were SARS-CoV-2 positive) infiltrating the lamina propria were found with no significant mucosal damage.Conclusions. We first report the direct evidence of active SARS-CoV-2 replication in a patient's rectum during the incubation period, which might explain SARS-CoV-2 fecal-oral transmission.