Q&A: We must ‘outsmart the virus’: Strategy needed to curb risk for long COVID, GI issues
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Infection with SARS-CoV-2 increased the risk for long-term gastrointestinal problems within 1 year, including motility disorders, acute pancreatitis and liver disease, according to a study published in Nature Communications.
“There are a lot of different hypotheses to explain why SARS-CoV-2, which we all thought of as a respiratory virus that leads to pneumonia or other respiratory problems, can actually result in GI disorders,” Ziyad Al-Aly, MD, chief of research and development service at Veterans Affairs St. Louis Health Care System and clinical epidemiologist at Washington University in St. Louis, told Healio.
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Using the U.S. Department of Veterans Affairs national health care database, Al-Aly and colleagues established a cohort of 154,068 patients who tested positive for COVID-19 between March 2020 and January 2021 and compared them with more than 11 million contemporary (people with no evidence of infection) and historical (people from before the pandemic) controls to predict the risks and 1-year burden of specific GI outcomes.
Results demonstrated that beyond the first 30 days of infection, patients with COVID-19 had a higher risk for GERD, peptic ulcer disease, acute pancreatitis, functional dyspepsia, acute gastritis, irritable bowel syndrome and cholangitis, as well as common digestive symptoms.
Further, the risk for any GI outcome was higher in the COVID-19 group (HR = 1.36; 95% CI, 1.34-1.39) compared with the contemporary control group, a finding that was consistent with the historical control group.
Healio spoke with Al-Aly about long-term GI disorders related to COVID-19 infection and the need for a sustainable strategy to protect against the virus.
Healio: Why do you think COVID-19 is causing long-term GI problems?
Al-Aly: We have known for a while that people present with GI problems, and there are multiple hypotheses to explain this. One is that the virus itself might reside in the gut, which might serve as a viral reservoir for SARS-CoV-2. Then, because the virus is there and could be replicating, it might lead to the variety of GI disorders we are seeing.
Another hypothesis is that of microbiome dysbiosis. There are actually many bacteria in the gut — more bacteria than human cells. When there is a viral infection, the virus disturbs that homeostasis, that habitat, the composition of bacterial cells in the gut, and that may lead to a state of disease. Other hypotheses involve dysfunctional immune system or auto-immunity and chronic inflammation.
Healio: Do you think the GI effects will be permanent?
Al-Aly: It is hard to tell at this point. Our study is for the first year after infection. We know now that many people have long-term problems, but we do not know at this point whether some conditions will subside at 18 months, at 2 years, at 3 years, or whether they could become permanent.
We have been dealing with COVID for only 3-plus years now. We have not been dealing with it long enough to know if this it is going to be a 5- or 10-year problem or even a lifetime problem.
There is some uncertainty regarding how long symptoms will persist in people with long COVID. Anecdotally, I can tell you that some patients do experience improvement over time and others do not, meaning that some patients still have problems 2 years out.
The silver lining, or potentially optimistic thinking, is that these conditions we have described in the GI tract are treatable and manageable.
Healio: Were you surprised by any findings in this study?
Al-Aly: If you had asked me this question 2 years ago, I would have said why would SARS-CoV-2, a respiratory virus, wreak havoc in so many organ systems? But having been doing an extensive amount of research on COVID and long COVID for the past 3 years, I cannot say that I am surprised.
These are people who are suffering from abdominal pain, constipation, diarrhea, pancreatitis, liver disease, IBS, etc. It is still sobering to see the extent of damage that SARS-CoV-2 can produce. It is a sad reality. But it is no longer surprising to me.
Healio: What additional research will you pursue on long COVID?
Al-Aly: We are interested in following people over time. Does it persist for a long period of time or does it improve in some people? We are collecting data for 18 months, 2 years. We are trying to understand the effect of variants and factors that could determine who is more at risk for these conditions. We are intensely working on this to try to develop a deeper understanding of long COVID.
Healio: Do you think there will ever be a vaccine to prevent long COVID?
Al-Aly: It is clear to me that the best protection from long COVID is protection from COVID itself. This emphasizes the need for vaccines that block transmission of COVID-19, so you do not have to rely on a mask to protect yourself. Instead, you would have a nasal vaccine that protects your airways from SARS-CoV-2.
We need an updated vaccine strategy that blocks transmission of the virus and reduces our reliance on nonpharmaceutical interventions to block entry of the virus. We also need vaccines that last longer. We have seen in our patients and throughout the nation that people are tired of getting boosters every now and then. They want a vaccine that you get once every 5 years, like the pneumonia vaccine, and it protects for a long time.
Finally, we need a variant-proof vaccine. What we have learned about this pandemic is that the virus is outsmarting us and outpacing us. It is mutating rapidly. By the time we rolled out the vaccine that covered the BA.4 and BA.5 Omicron variants, they were on the decline in the United States.
We need to outsmart the virus with a long-term sustainable strategy. We need a vaccine approach that reduces or blocks transmission, is more durable and is variant proof.
References:
- COVID-19 infections raise risk of long-term gastrointestinal problems. https://medicine.wustl.edu/news/covid-19-infections-raise-risk-of-long-term-gastrointestinal-problems/. Published March 7, 2023. Accessed March 16, 2023.
- Xu E, et al. Nat Commun. 2023; doi:10.1038/s41467-023-36223-7.
- Al-Aly Z, et al. Nature Medicine. https://www.nature.com/articles/s41591-022-01840-0.
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