It seems like new information is coming out daily about the relationship of COVID-19 to the gut, and I’m trying to stay on top of it as best as I can for us all. On Monday of this week, I spotted an article on Bloomberg about a new study out of a Hong Kong university, stating that the virus may linger in the gut long after it has cleared the respiratory system.[i] The actual study was conducted last February on 73 patients, more than half of whom tested positive for the virus in their stool. The scientists zeroed in on 15 of these positive cases to better understand what was happening, in terms of viral activity.
Interestingly, while active in the gut, the virus caused no GI symptoms in 7 of these people. And it remained active 7 days after respiratory samples were negative; in 1 patient, in fact, they found active virus in the gut 30 days after respiratory tests were negative. Whether or not stool is a means of transmission is being further tested. According to the lead researcher on this paper the gut bacteria of patients with GI COVID infection show a loss of protective bacteria and a proliferation of disease-causing ones, and this was worsened in those patients who were treated with antibiotics. He suggests that probiotics may be helpful in treating COVID. (Remember this blog post of mine from August 6th?)
On Wednesday, I found an article on News Medical about another paper just out that presents a host of new and interesting findings.[ii] Researchers at the Mount Sinai School of Medicine found that 60% of patients hospitalized with the virus have GI symptoms. They looked at 44 patients in their hospital during the peak of the pandemic here in New York, and collected stool samples during the acute and the convalescent phases of the infection.[iii] (Interestingly, re: my previous post on COVID, half the patients were characterized as obese and 70% had high blood pressure. There is no controversy over this: higher levels of systemic inflammation make you more prone to more severe COVID infection.) 70% of the patients studied had GI symptoms, mainly diarrhea. Some had nausea and vomiting. 41% of patients tested positive for the virus in their stools, and it was found more frequently in those with GI symptoms than without. That makes sense, and the numbers look similar to the Hong Kong study.
Here is where things get wonky. These scientists found that more patients without GI symptoms required admission to the ICU: 54% of them, versus only 19% of patients who did have GI symptoms. Weird, right?! It turned out that inflammatory markers were lower in those with GI symptoms, although this did not reach statistical significance. Unlike the study out of Hong King, they found that those with negative respiratory tests did not have detectable viral RNA in their feces. They DID find, however, that those who died of COVID had much higher viral loads in their feces than did the survivors, and that inflammatory cytokines were elevated in COVID patients – as is seen in other intestinal infections and inflammatory conditions – but that these did not associate with actual GI symptoms. Unlike the Hong Kong study, they found no specific microbiome alterations in the population. And finally, they found lower levels of regulatory cytokines (i.e. the off-switch to the inflammatory response) in the stool than of those severely infected.
So the biggest mystery, as far as I’m concerned, is why would it be that a “…significantly lower proportion of patients with GI symptoms were admitted to the ICU compared with those without GI symptoms”? There were no significant differences in blood markers for inflammation between the two groups. (What they did find, consistent with prior research, is that the more severe the disease presentation, the higher the levels of inflammatory cytokines found in the blood.)
Their conclusion is that while there is massive systemic inflammation in those with severe COVID, “…our data suggests that the gut can be an immunologically active organ during SARS-CoV-2 infection, as evidenced by virus-specific IgA, but there is little evidence for overt intestinal inflammation, even in patients with diarrhea or other GI symptoms.”
As soon as I finished writing this post for the first time, I found yet another article on COVID and the gut, this one on Gut Microbiota for Health[iv] , so just a couple more points. The authors of this article reiterate that some studies have shown bacterial alterations in those with COVID, and they point to two meta-analyses (here and here) showing the efficacy of probiotics in reducing the incidence, and the duration, of viral infections. (This, on top of the clinical trial I wrote about previously.)
The article points out that China’s National health commission and National Administration of Traditional Chinese Medicine both now recommend probiotics for the treatment of severe COVID. This is not, however, an accepted practice yet in the Western world. However, in light of the fact that we now know that what causes severe illness and death from COVID is actually a monster inflammatory response (cytokine storm), and at least 70% of the immune system is in the gut, the authors of this article state, “…one might argue that gut microbiome-immune system crosstalk could work as a team to normalize host immune response…”
I don’t know what to make of it all. Hopefully, we’ll get some more answers in the near future.
[iii] Britton, G. J. et al. (2020). SARS-CoV-2-Specific IgA And Limited Inflammatory Cytokines Are Present In The Stool Of Select Patients With Acute COVID-19. medRxiv preprint. doi: https://doi.org/10.1101/2020.09.03.20183947. https://www.medrxiv.org/content/10.1101/2020.09.03.20183947v1