SARS-CoV-2-Positive Sputum and Feces After Conversion of Pharyngeal Samples in Patients With COVID-19.

Abstract

Letters16 June 2020SARS-CoV-2–Positive Sputum and Feces After Conversion of Pharyngeal Samples in Patients With COVID-19FREEChen Chen, PhD, Guiju Gao, MD, Yanli Xu, MD, Lin Pu, MD, Qi Wang, MD, Liming Wang, PhD, Wenling Wang, PhD, Yangzi Song, MS, Meiling Chen, MS, Linghang Wang, MD, PhD, Fengting Yu, MS, Siyuan Yang, MS, Yunxia Tang, PhD, Li Zhao, PhD, Huijuan Wang, PhD, Yajie Wang, PhD, Hui Zeng, MD, PhD, and Fujie Zhang, MD, PhDChen Chen, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Guiju Gao, MDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Yanli Xu, MDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Lin Pu, MDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Qi Wang, MDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Liming Wang, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Wenling Wang, PhDNHC Key Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (W.W., L.Z., H.W.)Search for more papers by this author, Yangzi Song, MSBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Meiling Chen, MSBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Linghang Wang, MD, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Fengting Yu, MSBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Siyuan Yang, MSBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Yunxia Tang, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Li Zhao, PhDNHC Key Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (W.W., L.Z., H.W.)Search for more papers by this author, Huijuan Wang, PhDNHC Key Laboratory, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China (W.W., L.Z., H.W.)Search for more papers by this author, Yajie Wang, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, Hui Zeng, MD, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this author, and Fujie Zhang, MD, PhDBeijing Ditan Hospital, Capital Medical University, and Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China (C.C., G.G., Y.X., L.P., Q.W., L.W., Y.S., M.C., L.W., F.Y., S.Y., Y.T., Y.W., H.Z., F.Z.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0991 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: The outbreak of coronavirus disease 2019 (COVID-19) has become a global public health problem. In the absence of a specific therapy or vaccine, timely diagnosis and the establishment of a sufficient isolation period for infected individuals are critical to containment efforts. Real-time quantitative fluorescence polymerase chain reaction (RT-qPCR) testing of respiratory specimens for SARS-CoV-2 RNA is currently used for case diagnosis and to guide the duration of patient isolation or hospital discharge (1). Specimens that are positive on RT-qPCR have, however, also been reported from blood (2), feces (3), and urine (4). Whether testing of multiple body sites is important when considering patient isolation has not been thoroughly studied.Objective: To assess the results of RT-qPCR for SARS-CoV-2 RNA of sputum and fecal samples from a group of patients after conversion of their pharyngeal samples from positive to negative.Methods and Findings: We retrospectively identified a convenience sample of patients admitted to Beijing Ditan Hospital, Capital Medical University, with a diagnosis of COVID-19 and paired RT-qPCR testing of pharyngeal swabs with either sputum or feces samples. A diagnosis of COVID-19 required at least 2 RT-qPCR–positive pharyngeal swabs, and patients underwent treatments as well as initial and follow-up testing of pharyngeal, sputum, or fecal samples at the discretion of treating clinicians. Hospital discharge required meeting 4 criteria: afebrile for more than 3 days, resolution of respiratory symptoms, substantial improvement of chest computed tomographic findings, and 2 consecutive negative RT-qPCR tests for SARS-CoV-2 in respiratory samples obtained at least 24 hours apart (1). We report the findings of patients with at least 1 initial or follow-up RT-qPCR positive sputum or fecal sample obtained within 24 hours of a follow-up negative RT-qPCR pharyngeal sample. The RT-qPCR assay targeted the open reading frame 1ab (ORF1ab) region and nucleoprotein (N) gene with a negative control. A cycle threshold value of 37 or less was interpreted as positive for SARS-CoV-2, according to Chinese national guidelines.Among 133 patients admitted with COVID-19 from 20 January to 27 February 2020, we identified 22 with an initial or follow-up positive sputum or fecal sample paired with a follow-up negative pharyngeal sample. Of these patients, 18 were aged 15 to 65 years, and 4 were children; 14 were male; and 11 had a history of either travel to or exposure to an individual returning from Hubei Province in the past month. Fever was the most common initial onset symptom. Five patients had at least 1 preexisting medical condition (Table). All patients met criteria and were discharged from the hospital.Table. Characteristics of 22 Patients With Confirmed COVID-19 Who Had a Positive RT-qPCR Result for SARS-CoV-2 in Fecal and/or Sputum Samples After a Negative RT-qPCR Result on Pharyngeal SwabWe collected 545 specimens from 22 patients, including 209 pharyngeal swabs, 262 sputum samples, and 74 feces samples (Figure). In these patients, sputum and feces remained positive for SARS-CoV-2 on RT-qPCR up to 39 and 13 days, respectively, after the obtained pharyngeal samples were negative.Figure. Results of nucleic acid testing in 22 patients with confirmed COVID-19 infection, by timing of symptom onset.Infection was confirmed by RT-qPCR assay of pharyngeal swabs, sputum samples, and feces samples. Day 0 is the day of symptom onset for each patient. Patient 2 had RT-qPCR positive sputum samples after negative pharyngeal samples (although not paired within 24 hours); he was discharged from the hospital on the basis of sequential negative samples. N = negative; NA = not available; P = positive; RT-qPCR = real-time quantitative fluorescence polymerase chain reaction. Download figure Download PowerPoint Discussion: Pharyngeal swabs are widely used to determine the appropriateness of a patient's discharge from the hospital and whether isolation continues to be required. We observed 22 patients who had positive RT-qPCR results for SARS-CoV-2 in the sputum or feces after pharyngeal swabs became negative. These findings raise concern about whether patients with negative pharyngeal swabs are truly virus-free, or sampling of additional body sites is needed. It is important to emphasize, however, that it is not known whether the positive RT-qPCR results for SARS-CoV-2 observed here indicate that a patient continues to pose a risk for infection to others. Related, positive throat samples (after negative samples) after hospital discharge have been reported (5).Limitations of our study are that it is based on a convenience sample and that serial samples were not obtained from each patient on a defined schedule. These results warrant further study, including the systematic and simultaneous collection of samples from multiple body sites and evaluation of infectious risk.References1. China National Health Commission. Chinese Clinical Guidance For COVID-19 Pneumonia Diagnosis and Treatment. 7th ed. 4 March 2020. Accessed at http://kjfy.meetingchina.org/msite/news/show/cn/3337.html on 22 March 2020. Google Scholar2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. [PMID: 31986264] doi:10.1016/S0140-6736(20)30183-5 CrossrefMedlineGoogle Scholar3. Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020. [PMID: 32159775] doi:10.1001/jama.2020.3786 CrossrefMedlineGoogle Scholar4. Wang L, Li X, Chen H, et al. SARS-CoV-2 infection does not significantly cause acute renal injury: an analysis of 116 hospitalized patients with COVID-19 in a single hospital, Wuhan, China. medRxiv. 27 February 2020. Accessed at www.medrxiv.org/content/10.1101/2020.02.19.20025288v1 on 24 March 2020. Google Scholar5. Lan L, Xu D, Ye G, et al. Positive RT-PCR test results in patients recovered from COVID-19. JAMA. 2020. [PMID: 32105304] doi:10.1001/jama.2020.2783 CrossrefMedlineGoogle Scholar Comments0 CommentsSign In to Submit A Comment Neelesh GuptaUniversity of South Alabama Medical Center, Mobile, AL, USA1 April 2020 What about transmission Good to peruse this erudite study. The infectivity of sputum is of concern if the infection is air-borne like tuberculosis, and infectivity of stool is of concern only if the COVID-19 virus is not destroyed by gastric juices. Could authors shed light on these important issues. Disclosures: Nil Richard M Fleming, PhD, MD, JD (FHHI-OI-Camelot); Matthew R Fleming, BS, NRP (FHHI-OI-Camelot); Tapan K Chaudhuri, MD (Eastern Virginia Medical School)FHHI-OI-Camelot; Eastern Virginia Medical School31 March 2020 CoVid-19 Pneumonia Deaths - Exactly as defined - It’s time to get serious about this! The deaths associated with CoVid-19 are exactly as we have previously defined and warned about [1].The inflammatory reaction precipitated by viruses - worsening coronary artery disease (CAD), cancer, and other chronic inflammatory diseases - was originally laid out in the mid-1990s, published in a Cardiology Textbook in 1999 [2] and later detailed on 20/20 [3] in 2004.The inflammatory changes, which occur within tissue can and must be measured to determine the severity of CoVid-19 pneumonia (CVP). FMTVDM must also be used if we are to measure the success or failure of proposed treatments for CVP [4-6] - directing individual patient treatment; saving time, money, resources and lives.You need only ask yourself if guessing is good enough [7] or should we be measuring treatment outcomes? Simply ask yourself, what would you want if the patient with CVP on a ventilator in a hospital were your friend or someone you loved?