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.
We 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.
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.
CoVid-19 Pneumonia Deaths - Exactly as defined - It’s time to get serious about this!
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?
References:
1. Fleming RM, Fleming MR, Chaudhuri TK. Hope and knowledge, after all, is very contagious – more contagious than this virus. 18 March 2020. BMJ 2020;368:m1087. https://www.bmj.com/content/368/bmj.m1087/rr
2. Fleming RM. Chapter 64. The Pathogenesis of Vascular Disease. Textbook of Angiology. John C. Chang Editor, Springer-Verlag New York, NY. 1999, pp. 787-798. doi:10.1007/978-1-4612-1190-7_64.
3. “Hidden Heart Disease. Could a simple, inexpensive test save your life?” 20/20 - ABC Network with Barbara Walters and Dr. Timothy Johnson 16 April 2004. https://www.youtube.com/watch?v=Hvb_Ced7KyA&t=22s
4. The Fleming Method for Tissue and Vascular Differentiation and Metabolism (FMTVDM) using same state single or sequential quantification comparisons. Patent Number 9566037. Issued 02/14/2017.
5. Mahase Elisabeth. Covid-19: what treatments are being investigated? BMJ 2020; 368:m1252
6. Sayburn Anna. Covid-19: trials of four potential treatments to generate “robust data” of what works BMJ 2020; 368 :m1206
7. Fleming RM, Fleming MR, Dooley WC, Chaudhuri TK. Invited Editorial. The Importance of Differentiating Between Qualitative, Semi-Quantitative and Quantitative Imaging – Close Only Counts in Horseshoes. Eur J Nucl Med Mol Imaging. 2020;47(4):753-755. DOI:10.1007/s00259-019-04668-y. Published online 17 January 2020 https://link.springer.com/article/10.1007/s00259-019- 04668-y https://rdcu.be/b22Dd
Disclosures: FMTVDM issued to first author.
What about transmission
Disclosures: Nil
Time to advocate for Stool testing in hospitalized COVID-19 patients
To the Editor:
Dr. Chen and colleagues1 published on the detection of SARS-CoV-2 in the sputum or feces up to 39 and 13 days, respectively, after pharyngeal swabs became negative. This finding adds to growing evidence of prolonged viral shedding beyond the recommended isolation period for patients. To better understand fecal-oral and fecal-respiratory routes of transmission and to improve infection control strategies, we believe it’s time to time to advocate for Stool testing in hospitalized COVID-19 patients.
Existing data report increased prevalence of GI symptoms up to 12% of COVID-19 patients, with viral shedding observed in 40.5% of all patients2 . In a systematic review by Cheung et al., fecal viral shedding was reported in 70.3% of patients after respiratory specimens became negative3. Xiao et al. were able to isolate the SARS-CoV-2 virus from feces on two viral-RNA-positive patients, and the authors were able to show that the isolated virus was infectious to susceptible cells and could be neutralized by antibodies when the sample is exposed to the patient’s serum4. This result may suggest evidence of fecal-oral transmission or fecal-respiratory transmission through aerosolized feces. Furthermore, on April 9, 2020 Food and Drug Administration (FDA) released a safety alert on the potential risk of transmission of SARS-CoV-2 by fecal microbiota for transplantation (FMT)5.
Up-to-date isolation guidelines may be inadequate to mitigate the spread of infection in both clinical and community settings and thus we want to emphasize the following points:
Based on current data, we urge for the expansion of our testing of viral RNA detection to stool samples to understand viral shedding dynamics better. As hospitalists we recognize the limitations of current testing capabilities, feasibility to perform stool testing in all COVID-19 patients. However, a rigorous approach, such as stool testing in addition to nasopharyngeal swab testing to confirm disease recovery, may have implications, especially in moderate and severe covid-19 patients require hospitalization. Hospitalized patients who require gastrointestinal interventions, intraabdominal surgical procedures, and care transition, discharging patients to long term or short term health facilities.
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Disclosures:
NA
Time to advocate for stool testing in hospitalized COVID-19 patients.
Thank you for your comments and continuous interest in our study. In addition to our observation on the positive test of SARS-CoV-2 in feces, authors noticed that the virus was isolated from feces and present as a high prevalence 1. Thus, it is important to understand the fecal-oral and fecal respiratory routes of transmission.
Currently, the commonly recognized transmission route of COVID-19 is through droplets by airway breathing and close contact via contaminated hands2. Several recent outbreaks provided the contaminant food may also cause the infection, especially the reemergence of SARS-CoV-2 in Beijings Xinfadi Wholesale Market after 56 days silent of the virus3. Sparking concern that salmon could be contaminated with the deadly virus, and whether SARS-CoV-2 could transmitted from fish to humans is unclear. These evidences raised the potential risk of fecal-oral and fecal-respiratory transmitted routes in addition to respiratory route of SARS-CoV-2.
There is dearth evidence to support the fecal-oral or fecal-respiratory transmission yet. Limited data of epidemic surveillance of SARS-CoV-2 in feces has been illustrated4. In our hospital, lack of the human source in clinic, the epidemic surveillance of SARS-CoV-2 in feces is still not carried out. However, there are increasing studies reporting GI manifestations among patients infected with COVID-19 especially among those who turned to be negative in pharyngeal swabs suggesting that the SARS-CoV-2 in not only confined to the lung but also to the other parts of respiratory tract and gastrointestinal system5.
In addition, our recent study demonstrated two SARS-CoV-2 variant types co-infected in one patient, but might lead to different organs, subsequently. The further tropism of SARS-CoV-2 in gastrointestinal tract and respiratory tract should be cared for. These mutants of virus might play important roles for virus to evade the host immunity under different immune selective pressure.
We agree it is time to conduct more research on exploration of consolidate evidence to support the establishment of other transmission route other than respiratory transmission. Under current situation without consolidate evidence of fecal-oral or fecal-respiratory transmission, stools monitoring is necessary to either for the confirmation of disease recovery or for the determination of the isolation.
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