Jennifer Huizen

Respiratory symptoms are the most common symptom of COVID-19.

But according to a recent review, 53 percent of people hospitalized with COVID-19 experience at least one gastrointestinal (GI) symptom at any time during their illness.

And there’s increasing evidence that encountering GI symptoms with COVID-19, or developing COVID-19 alongside underlying GI conditions, may increase the risk of disease severity and negative complications.

GI symptoms associated with COVID-19

Respiratory symptoms, such as coughing or trouble breathing, are the most common symptoms of COVID-19.

But early reports out of China made it clear that COVID-19 can also trigger GI system symptoms. The GI system includes:

• the mouth
• esophagus, the tube that connects to the stomach
• stomach
• small and large intestines
• the anus

The first person with confirmed COVID-19 in the United States also experienced 2 days of nausea and vomiting before developing diarrhea. And one of the earliest American studies found that around 32 percent of patients with the disease experienced diarrhea, nausea, or loss of appetite.

The research is ever-evolving. But according to a review published this month analyzing 125 articles and a total of 25,252 patients, the most common GI symptoms associated with COVID-19 include:

• lack of appetite (19.9%)
• lack of smell or taste (15.4%)
• diarrhea (13.2%)
• nausea (10.3%)
• vomiting up blood or GI bleeding (9.1%)

Another review published in late January found much broader ranges of symptom prevalence rates, such as:

• diarrhea (9–34%)
• nausea, vomiting, or both (7–16%)
• abdominal pain (3–11%)
• Less commonly, COVID-19 may also cause:
• belching
• acid reflux
• indigestion
• colitis, or intestinal inflammation
• GI bleeding

The disease may also destroy bowel tissues and reduce intestinal movement.

Right now, it seems most people who experience GI symptoms with COVID-19 develop them alongside respiratory symptoms.

However, a review from late 2020 found around 20% of people with COVID-19 infections only experience GI symptoms. And sometimes, these symptoms develop before respiratory symptoms or fever develop.

Early studies suggest GI symptoms tend to occur during the early stages of the infection. But more research is needed to confirm when GI symptoms develop in COVID-19 cases if there is a specific time frame.

 How COVID-19 causes GI symptoms

Researchers are still learning more about how infection with SARS-CoV-2 affects different parts of the body.

There is evidence that SARS-CoV-2 can infect cells in the respiratory and GI tract, as well as cells in other locations in the body.

Most studies show the SARS-CoV-2 virus enters intestinal cells, or enterocytes, and respiratory cells using the angiotensin-converting enzyme 2 (ACE-2) protein as a receptor. The ACE-2 receptor is embedded in cellular membranes. It helps regulate blood pressure by controlling levels of the protein angiotensin, which encourages blood vessels to constrict and raise blood pressure.

The virus enters intestinal cells after its characteristic spike proteins bind to ACE-2. Once inside the cell, the virus uses the cells’ own machinery to produce copies of viral proteins and ribonucleic acid (RNA). RNA is the genetic material of retroviruses, such as SARS-CoV-2, much like human DNA.

When SARS-CoV-2 particles leave an infected cell, it triggers the release of cytokines, small proteins that play a role in inflammation. This process may cause GI symptoms.

GI symptoms can also occur as viruses destroy or damage GI tissues, especially pain, nausea, and diarrhea. Some research shows that COVID-19 may also change the gut microbiota, the community of microbes that normally inhabit the intestines or stomach.

Once in the GI tract, the virus can also travel through the portal vein, the vein that drains blood from the digestive tract. This can allow viruses to impact the vagus nerve, causing a nauseous sensation.

Nausea and diarrhea are also common symptoms of medications that healthcare professionals often use to manage COVID-19, such as antivirals and antibiotics.

There is increasing evidence that SARS-CoV-2 could pass on to others via fecal-oral transmission. This means people could acquire an infection by accidentally consuming or inhaling droplets of infected feces.

In fact, fecal samples from the first person with confirmed COVID-19 in the U.S. contained virus particles. Other coronaviruses can also cause viral shedding, referring to the release of viral particles in feces.

Some research even suggests people may shed viral particles in their feces after the virus is undetectable in the upper respiratory system, such as the lungs, nose, or throat.

If true, this could change how someone can spread the virus to others and for how long. But researchers have yet to determine whether the proteins and particles shed in feces are infectious, or capable of actually causing disease.

GI symptoms and disease outcomes

People who experience GI symptoms with COVID-may be more likely to develop negative health complications or risks.

A study from November 2020 found experiencing these symptoms heightened the risk of developing acute respiratory distress syndrome, as have several studies since then.

The study also found that experiencing GI symptoms increased the risk of undergoing procedures with major health risks, such as noninvasive mechanical ventilation and tracheal intubation.

And a report from October 2020 found children with COVID-19 who develop GI symptoms were more likely to experience severe, critical infections and cardiac impairments.

Another study from late January 2021 concluded that experiencing these symptoms also seems to increase the likelihood of developing severe disease and dying in adults. An even more current review found people with COVID-19 and GI symptoms on admission to the hospital were also more likely to develop acute heart and kidney damage or die from the disease.

Dozens of studies have also found that people with preexisting GI conditions are more likely to experience serious disease and negative complications.

Research published this month found people with GI conditions, such as Barrett’s esophagus, seem to be at an increased risk of developing severe COVID-19 symptoms and disease.

Some researchers speculate this connection probably exists because GI diseases can cause intestinal metaplasia, which replaces the stomach lining with cells similar to intestinal lining cells.

Many GI conditions may also make it easier to develop GI infections because they damage or weaken the intestinal or stomach lining. Some of these conditions, such as irritable bowel syndrome, also cause the over-expression of ACE-2, giving viruses more opportunities to enter cells.

Medications used to treat GI diseases or symptoms can also reduce stomach acid levels, making it easier to contract the virus from foods or other ingested substances. Normally, the stomach’s high acidity levels are strong enough to deactivate viral particles.

Less speculation exists as to why experiencing GI symptoms with COVID-19 seems to increase the risk of severe disease and poor outcomes in the absence of underlying conditions.

People with viral infections in their respiratory and GI tract are exposed to increased viral load when compared with people with infections in only the respiratory tract.

There are also around 100 times more ACE-2 receptors in the GI tract than respiratory organs, so it may be able to house more viruses when it acquires an infection.

People with symptoms impacting multiple organs also tend to experience more severe disease and poorer outcomes.

Early evidence seems consistent. But a wider scale, long-term studies need to determine the true relationship between GI symptoms, GI conditions, and COVID-19.

For example, some research indicates people who develop GI symptoms with COVID-19 may actually experience milder disease.

Remaining questions

Knowing how often, when, and why COVID-19 causes GI symptoms could have significant benefits.

If these symptoms are as common as research shows, doctors and nurses could start testing people with these indicators, namely loss of smell and taste, fever, anorexia, and diarrhea, as highly specific for COVID-19 infection — even in people without respiratory symptoms. This could help identify potentially millions of COVID-19 cases earlier, including otherwise asymptomatic cases.

Tracking GI symptoms in a population may also help identify disease outbreaks before they occur.

A study comparing rates of internet searches for these symptoms commonly associated with COVID-19 in 15 states found that, in some states, surges in searches occurred 3–4 weeks before surges in case levels.

Researchers also need to know if preexisting GI diseases increase the risk of developing severe disease, negative complications, and dying. They will also have to figure out whether GI conditions make someone more susceptible, or prone, to developing COVID-19. This could teach healthcare professionals how to handle potential, active, or resolved cases of COVID-19 in people with GI diseases better.

It will also be important to learn whether COVID-19 can spread through feces and how long someone remains contagious.

In a review from early February, feces samples from 26.7% of individuals with confirmed COVID-19 contained viral RNA and shed infective particles for roughly 19 days.

If the disease can spread through feces, this could change current hygiene and self-isolation recommendations.

The Centers for Disease Control and Prevention (CDC) currently also only recommend people self-isolate for 10–20 days after symptom onset. If someone’s feces remain capable of spreading infection for longer, public health bodies may have to consider reviewing their guidelines.

If feces containing the new coronavirus can spread the infection, it will also be important to monitor and potentially treat wastewater to reduce transmission. The CDC already have the tools to help states create their own surveillance sampling strategies.

Researchers also need to learn more about the long-term GI impacts associated with COVID-19.

Some preliminary studies show certain symptoms may persist for weeks to months after recovering from the disease. A recent review found approximately 16% of people may still experience nausea and vomiting after recovering, while 12% may continue to experience digestive disorders.

It will take time to truly uncover when and why COVID-19 triggers GI symptoms, and how they impact disease severity and outcomes. And it will likely take much longer to figure out if, and how often, symptoms become long-term.

But as daunting as it sounds, this knowledge could bring about substantial improvements in how we diagnose, treat, monitor, and track COVID-19.- Medical News Today