key: cord-1053127-v4c1lgpd
authors: Wang, Xiaorong; Zhou, Yaya; Jiang, Nanchuan; Zhou, Qiong; Ma, Wan-Li
title: Persistence of intestinal SARS-CoV-2 infection in patients with COVID-19 leads to re-admission after pneumonia resolved
date: 2020-04-27
journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
DOI: 10.1016/j.ijid.2020.04.063
sha: b4fa788bb6dcb89135d09b0611e9d99f8f2559fc
doc_id: 1053127
cord_uid: v4c1lgpd

Abstract The current reports of COVID-19 focus on the respiratory system, but intestinal infections caused by SARS-CoV-2 are also worthy of attention. Here we report persistence of intestinal SARS-CoV-2 infection in three cases with COVID-19 leads to re-admission after pneumonia resolved.

Outbreak of the novel coronavirus disease caused by severe acute respiratory syndrome coronaviruse-2 (SARS-CoV-2) in Wuhan City, Hubei Province, China, has been rapidly spreading nationwide and abroad. Studies demonstrated that SARS-CoV-2 enters into human cells through human angiotensin-converting enzyme 2 (ACE2) as it's receptor which was highly expressed not only in type II alveolar epithelial cells (AT2), but also in absorptive enterocytes from ileum and colon (Zhang et al., 2020) . Besides the common symptoms included fever, fatigue, and dry cough, gastrointestinal symptoms were also occurred in some patients with COVID-19 (Wang et al., 2020; Chen et al., 2020) , additionally, researchers had tested and isolated viable SARS-CoV-2 from stool (Holshue et al., 2020; World Health Organization, 2020; Pan et al., 2020) . Those demonstrated that digestive system is a potential route for SARS-CoV-2 infection. However, previous clinical diagnosis and discharge criteria were mainly based on respiratory system (National Health Commission of the People's Republic of China, 2020), and studies of the enteric involvement and viral excretion of SARS-CoV-2 in faces as well as the influences of gastrointestinal infected SARS-CoV-2 on the disease course were not available (Yeo et al., 2020) . Here, we reported 3 cases who were discharged meeting for all of the hospital discharge criteria (National Health Commission of the People's Republic of China, 2020) were admitted again may due to the persistence of intestinal SARS-CoV-2 infection.

All the following criteria had to be met for hospital discharge of the three cases: (1) normal An evaluation version of novaPDF was used to create this PDF file. Purchase a license to generate PDF files without this notice. Table 1 ), diarrhea 10-12 times per day, the oxygen saturation values dropped to 94%. On illness day 10, she received arbidol and interferon as well as probiotics including yeast and bifidobacterium. All symptoms with the exception of loose stool 2-3 times per day and the lesions in chest CT had resolved (Figure 1) , besides, the throat swabs specimens for SARS-CoV-2 were negative on illness day 24 and 26. The patient was discharged on illness day 28. However, one day after discharge, the patient had fever combined with fatigue and watery diarrhea 6-7 times per day and was admitted again. Laboratory results reflected leukopenia (Supplementary Table 1 negative and all symptoms have resolved, the patient discharged again, we telephoned follow-up, the patient did not report special discomfort so far.

Case 2: A 30-year-old female presented of diarrhea with yellow watery stools 3-5 times per day combined with changes in bowel habits (defecating after diet) on January 23, 2020, seven An evaluation version of novaPDF was used to create this PDF file. Purchase a license to generate PDF files without this notice. Case 3: A 24-year-old female with confirmed COVID-19 presented with intermittent fever, nasal congestion, cough, fatigue, anorexia and lost her sense of smell was treated in hospital.

On admission, she received arbidol and interferon for five days. Her temperature turned to normal on illness day 24 and symptoms gradually improved (Supplementary Figure 1C) . The throat swabs for SARS-CoV-2 turned negative on illness day 26, 28 and her chest CT improved ( Supplementary Figure 2) , while the stool was positive for SARS-CoV-2 without any digestive symptoms on illness day 24, 26 and 30. The patient discharged on illness day 31. However, one day after discharge, the patient appeared fever combined with nausea, vomiting and diarrhea with yellow watery stools 5 times per day, the laboratory results reflected leukopenia again (Supplementary Table 3 ), chest CT was resolved fully, the throat swabs were negative but the stool samples were still positive for SARS-CoV-2 by RT-PCR.

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J o u r n a l P r e -p r o o f 6 We reported three SRAS-CoV-2 confirmed patients with persistence of gastrointestinal symptoms and detective SARS-CoV-2 RNA in stool samples to re-admit after SARS-CoV-2 pneumonia resolved. We speculate that persistence of intestinal infection caused by SARS-CoV-2 leads to re-admit at the first discharge or time of waiting for discharge.

In early reports from Wuhan, China, the most common symptoms of COVID-19 included fever, fatigue, dry cough and shortness of breath, and the chest CT images showed lesions in the lungs of all patients, and only 2-10% of patients with COVID-19 had gastrointestinal symptoms such as diarrhea, abdominal pain, and vomiting (Wang et al., 2020; Chen et al., 2020) . The three patients who mainly presented with gastrointestinal symptoms such as diarrhea and changes in bowel habits and positive for SARS-CoV-2 of stool samples were admitted again after negative SARS-CoV-2 for respiratory specimens and chest CT images resolved, demonstrating the digestive system may be the main target organ of SRAS-CoV-2 in the three patients and the viral load in faces at the very low-risk status when COVID-19 patients are discharged from hospital. Those highlight clinicians should pay much attention to managing digestive symptoms of patients with COVID-19 properly.

The diseases course of the three patients were more than 30 days which were much longer than the whole patients with COVID-19 we analyzed earlier (unpublished data) which was 21 days on average from illness onset to discharge, and was also longer than that of patients Recent evidence reveals that fecal nucleic acid is readily detected in the stool and rectal An evaluation version of novaPDF was used to create this PDF file. Purchase a license to generate PDF files without this notice. swabs of patients with COVID-19 (Holshue et al., 2020; Zhang et al., 2020) , combining with our present cases, the environmental contamination by faces and induce aerosolization transmission of patients with COVID-19 should be paid much attention. However, our report have limitations about that the presence of SARS-CoV-2 nucleic acid in stool alone cannot be used to define infection and transmission, and further studies about influences of the enteric involvement and viral excretion of SARS-CoV-2 in faces on transmission dynamics of SARS-CoV-2 are worthy of further study.

Up to now, both diagnostic and discharge criteria of COVID-19 were based on the symptoms and manifestations of the respiratory system (National Health Commission of the People's Republic of China, 2020), however, some patients may present with mainly digestive symptoms due to gastrointestinal tract infected by SARS-CoV-2. So, current criteria for hospital discharge and continued patient management may need to be reevaluated.

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