By Suzanne Devkota, PhD, Cedars-Sinai Medical Center; Member, AGA Center for Gut Microbiome Research & Education Scientific Advisory Board
There is no question that COVID-19 is primarily a respiratory disease with the majority of complications leading to death: pneumonia, hypoxic respiratory failure or acute respiratory disease syndrome, affecting the lungs. However, several reports from China and emerging data from other international sites have reported subgroups of COVID-19 patients with the following: 1) concurrent gastrointestinal symptoms, notably diarrhea; 2) onset of GI symptoms prior to respiratory symptoms; or 3) GI symptoms in the absence of respiratory symptoms.1-3 These studies have also found that concurrent GI symptoms relates to severity of COVID-19 disease, and duration of viral shedding.2
There is also strong data showing that the virus sheds in the stool ranging from day one of onset of symptoms to day 28.3-5 These findings, while widely discussed in the GI community, have only been touched upon in the mainstream press. The value of this data, however, could be critical to helping contain the spread of SARS-CoV-2.
A key question that remains is whether the virus shedding in stool is from live or dead virus. Given the high expression of ACE2 receptor (the cellular receptor for SARS-CoV-2) in the intestinal epithelium, it is highly plausible that the gut is a site of active viral replication.
It seems like an easy question to answer, however, the methods for this are complex. Viruses by definition need a host cell to replicate. Therefore, unlike bacteria which we can grow independently in nutrient-rich broth, viral propagation requires infecting cell lines with live virus obtained from a biological specimen. A viral plaque assay, such as this, is generally the gold standard. However, the CDC requires BSL-3 level containment to work with live SARS-CoV-2, which many labs and institutions do not have available for research, if at all. An alternative method to assess active viral replication without live virus is to assay for viral sub-genomic mRNA (sgmRNA). SgmRNA encodes conserved structural and accessory proteins but is not packaged into the new virion.
A study from Germany published as a pre-print in Nature, employed both methods in stool samples from COVID-19 patients and could not detect live virus in stool, however sgmRNA transcripts were detectible.6 It is important to note that these samples were only collected after day 6, which misses what is believed to be the most infectious window for this disease, and longitudinal sampling for these assays was only achieved in four patients.
Until more molecular data emerges assessing the infectivity of stool samples, clinicians should consider stool and other gut-derived samples from suspected and confirmed COVID-19 patients as infectious, with appropriate personal protective equipment made available just as would be made available for handling nasopharyngeal, sputum and saliva samples.
1. Wang, D., Hu, B., Hu, C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020; 323:1061.
2. Jin, X., Lian, J-S., Hu, J-H. et al. Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms. Gut 2020 Mar 24 [Epub ahead of print].
3. Lin, L., Jiang, X., Zhang, Z. et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut 2020 Apr 2 [Epub ahead of print].
4. Xiao, F., Tang, M., Zheng, X. et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology 2020 Mar 3 [Epub ahead of print].
5. Holshue, M.L., DeBolt, C., Lindquist, S. et al. First case of 2019 novel coronavirus in the United States. N Engl J Med 2020; 382:929–36.
6. Wölfel, R., Corman, V.M., Guggemos, W. et al. Virological assessment of hospitalized patients with COVID-2019. Nature 2020 Apr 1 [Epub ahead of print].