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Alternative Route Mechanisms of Covid-19

This post is written by FPA intern Avery Hill

The main focus of the novel coronavirus has been the respiratory system, but recent research indicates that the scope of viral transmission may extend to the human gastrointestinal tract. Research from Sun Yat-Sen University in China showed that out of 73 confirmed positive patients, 53.4% had viral RNA in their feces. Moreover, RT-PCR tests (reverse transcriptase-polymerase chain reaction - currently the most common testing technique for the novel coronavirus) showed that the patients could test positive for viral RNA in feces even after testing negative using respiratory samples. Outside of this study, it has been widely reported that coronavirus patients may suffer from a variety of non-respiratory symptoms including diarrhea, nausea, and abdominal pain, all linked to the GI tract.

While more evidence is needed, the data opens of the distinct possibility of fecal-oral transmission. The potential for this route of transmission is substantiated through research done on SARS-CoV and MERS-CoV, related coronaviruses. SARS-CoV can survive for up to five days after drying when temperature conditions are between 71-77oF and 40-50% relative humidity. Equally, MERS-CoV was found to be viable on different surfaces for 48 h at 20°C and 40% relative humidity. These findings suggest the extent of virus viability and indicate the plausibility of infection fecal-oral transmission.

Data also indicates that coronaviruses are able to survive in the stomach and cause infection through the intestinal epithelial cells. Research in 2012 from Saudi Arabia found that MERS-CoV proved to be ‘resistant’ in the stomach acid of someone who had recently eaten as it is more diluted. A University of Hong Kong study indicated that the human primary intestinal epithelial cells were extremely susceptible to MERS-CoV. It was shown that mice initially infected with MERS-CoV in the gut eventually showed evidence of live viruses in the lung tissues. The appearance of viruses in the lung cells indicates the development of a respiratory infection even though the virus was not initially present in the lung tissue. This research suggests the human intestinal tract may serve as a transmission route for MERS-CoV.

Currently, there is no viability data for SARS-CoV-2, so what is true for MERS-CoV and SARS-CoV may not be true for SARS-CoV-2. However, this research suggests that SARS-CoV-2 could potentially infect the gastrointestinal tract through the ACE2 protein receptors on the epithelial cells. Lung cells are the primary site of this protein but they are also abundantly present as specified in the gastrointestinal tract. If SARS-CoV-2 can cause infection through ACE2 proteins on lung cells, why not also in the intestinal epithelial cells of the gastrointestinal tract? The movement of MERS-CoV from the GI tract to the lungs in mice shows how it may be possible for SARS-CoV-2 to cause respiratory infection through fecal-oral transmission in a similar way. The potential of fecal-oral transmission has implications for food consumption and highlights the importance of hygienic food practices. However, no reported cases of SARS-CoV-2 being transmitted through food, and more data are needed to confirm this possibility.

There are interesting therapeutic implications of this theory as well. Research findings on coronaviruses open up new treatment possibilities for Covid-19. For example, FirstWave Bio, a biotech startup, initially used the small molecule Niclosamide as a potential IBD treatment. Now, Niclosamide has been repurposed in order to hinder the action of SARS-CoV-2. The group has announced plans to use a formulation of Niclosamide in a Phase 2a/2b trial to combat SARS-CoV-2. The company aims to start the clinical trial in the EU by mid-2020 and follow with a US trial. It will act directly in the gastrointestinal tract and will hopefully reveal more about the action pathways of the novel coronavirus. Research such as this may pave the way for alternative methods of treatment for coronaviruses and other diseases.

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