Direct evidence of active SARS-CoV-2 replication in the intestine.

BACKGROUND: Currently, there is no direct evidence to prove the active SARS-CoV-2 replication 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 clinically confirmed COVID-19 patient with rectal adenocarcinoma. METHODS: Here, the clinical data were collected during hospitalization and follow-up of this patient. Quantitative 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 on 37 day after discharge. Notably, coincidence with rectal tissues of surgical specimens tested nucleic acid positive for SARS-CoV-2, typical coronavirus virions in rectal tissue were observed under electron microscopy. Moreover, abundant lymphocytes and macrophages (some are SARS-CoV-2 positive) infiltrating the lamina propria were found with no significant mucosal damage. CONCLUSIONS: We firstly reported that direct evidence of the active SARS-CoV-2 replication in the patient's rectum during the incubation period, which might explain SARS-CoV-2 fecal-oral transmission.