American researchers have provided new insights to the understanding of the diarrhea pathophysiology in Covid-19 patients, suggesting it depends upon the inflammatory response of the body. The term “Covid-19 diarrhea” has lately emerged as a new symptom caused by the deadly virus, however, without knowing much about it previously, it was linked with stress, and anxiety and not the virus itself. This new study suggests that the coronavirus-linked diarrhea is the first of its kind viral diarrhea that is triggered by the inflammatory response of the body.
The research team from the Johns Hopkins University School of Medicine (Maryland) in collaboration with the Health Sciences Center at the University of New Mexico (Albuquerque) studied how inflammatory response triggers this Covid-19 diarrhea in the patients. They found that only one tiny change in the human intestinal transport system is involved in restricting NHE3 protein and DRA protein that further allows the body to absorb neutral sodium chloride (NaCl). That’s how the sodium in the intestine is completely absorbed between the main meals of the day.
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The chloride secretion is affected when the body activates the calcium-activated chloride channel (CaCC) using a mechanism called intracellular calcium ions (Ca 2+). So this Covid-19 diarrhea is caused by calcium-dependent inflammatory action.
This paper is currently under peer review but its pre-print form is available online, at the bioRxiv server. Click here to read it.
As we are heading ahead in this pandemic, the gastrointestinal covid-19 manifestations continue to increase including the previously acknowledges manifestations even those which are observed in the longer run (also called Long Covid). These manifestations also include diarrhea that mostly shows up during the early days of infection but it can show up at any stage or level of the infection including the prolonged period.
Interestingly these gastrointestinal manifestations were thought to be luminal and not the systematic association of the virus and gut. The study authors write that this virus can also be recovered from the intestines where it multiplies using the human enterocytes.
There is no clear evidence that helps understanding how the virus changes intestinal sites causing diarrhea and how this inflammatory response adds up to the chances of getting diarrhea. It is still a mystery that how the GI tract facilitates viral replication and continues the disease progression.
For this current study, the research team used a human enteroid model and some virus-like particles (VLPs) prepared from exosomes. After 48 hours of exposure, they studied how the replication has started in the enterocytes and the presence of the virus as well as viral RNA in basolateral media and apical media for up to five days.
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This whole mechanism of inducing Covid-19 diarrhea uses the molecular channels including the inflammatory cytokines, apical ion transport proteins, viral receptors, and basolateral ion transport proteins, along with Ca2+ signaling activation among the cells.
These findings are still awaiting a review but based on the findings, they seem to understand the Covid-19 to some extent, implying that it can show up at any stage of the infection, irrespective of the severity of Covid-19 symptoms.