What we know so far

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

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

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

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

Research is constantly evolving. But according to a review published this month that analyzed 125 articles and a total of 25,252 patients, the most common GI symptoms associated with COVID-19 are:

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

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

• diarrhea (9-34%)
• nausea, vomiting, or both (7-16%)
• abdominal pain (3-11%)

Less commonly, COVID-19 can also cause:

The disease can also destroy intestinal tissue and reduce bowel movement.

At this point, it appears that most people who experience GI symptoms with COVID-19 develop them in addition to respiratory symptoms.

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

Early studies suggest that 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.

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

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

Most studies show that 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 cell membranes. It helps regulate blood pressure by controlling levels of the protein angiotensin, which stimulates blood vessels to constrict and increase blood pressure.

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

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

Once in the gastrointestinal tract, the virus can also travel through the portal vein, the vein that drains blood from the digestive tract. This allows viruses to affect the vagus nerve, causing nausea.

Nausea and diarrhea are also common symptoms of medications commonly used by healthcare professionals to treat COVID-19, such as antivirals and antibiotics.

There is growing evidence that SARS-CoV-2 can be transmitted to others through faecal-oral transmission. This means that people can contract an infection by accidentally consuming or inhaling droplets of infected stool.

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

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

If this is true, it 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 that end up in the stool are contagious or can actually cause disease.

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

A November 2020 study found that experiencing these symptoms increased the risk of developing acute respiratory distress syndrome, as did 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 an October 2020 report found that children with COVID-19 who develop GI symptoms are more likely to have serious, critical infections and heart disorders.

Another study from late January 2021 concluded that experiencing these symptoms also appears to increase the chances of developing serious illness and death in adults. An even more current review found that when admitted to hospital, people with COVID-19 and GI symptoms were also more likely to suffer acute heart and kidney damage or death from the disease.

Dozens of studies have also shown that people with pre-existing gastrointestinal conditions are more likely to have serious illnesses and negative complications.

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

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

Many GI conditions can 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 ACE-2 overexpression, which makes viruses more likely to enter cells.

Medicines used to treat gastrointestinal disorders or symptoms can also lower stomach acid levels, making it easier to contract the virus from food or other ingested substances. Normally, the stomach’s high acidity is strong enough to inactivate viral particles.

There is less speculation as to why experiencing gastrointestinal symptoms with COVID-19 appears to increase the risk of serious illness and poor outcomes in the absence of underlying conditions.

People with respiratory and gastrointestinal viral infections are exposed to an increased viral load compared to people with respiratory infections alone.

There are also about 100 times more ACE-2 receptors in the gastrointestinal tract than respiratory organs, so it can potentially harbor more viruses when it catches an infection.

People with symptoms that affect multiple organs also tend to experience more serious illness and worse outcomes.

Early evidence seems consistent. But a broader, long-term study needs to determine the true relationship between GI symptoms, GI disorders and COVID-19.

For example, some research indicates that people who develop GI symptoms with COVID-19 may develop milder illness.

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

If these symptoms are as common as research shows, doctors and nurses can start testing people with these indicators, namely loss of smell and taste, fever, anorexia and diarrhea, just as specific for COVID-19 infection – even 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 can also help identify disease outbreaks before they occur.

A study comparing the percentages of Internet searches for these symptoms commonly associated with COVID-19 in 15 states found thatIn some states, peaks in queries occurred 3 to 4 weeks before peaks in case levels

Researchers also need to know whether pre-existing gastrointestinal conditions increase the risk of developing serious illness, negative complications, and death. They will also need to find out if GI conditions are making someone more or more prone to developing COVID-19. This could teach health care professionals how to better address potential, active, or resolved cases of COVID-19 in people with GI disease.

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

In an early February review, faecal samples from 26.7% of subjects with confirmed COVID-19 contained viral RNA and released infectious particles for about 19 days.

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

Also, the Centers for Disease Control and Prevention (CDC) currently only recommends that people isolate themselves 10 to 20 days after the onset of symptoms. If a person’s feces are able to spread infection longer, public health authorities may need to consider revising their guidelines.

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

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

Some preliminary studies show that certain symptoms can last for weeks to months after recovery from the disease. A recent study found that about 16% of people can still experience nausea and vomiting after recovery, while 12% can still suffer from digestive disorders.

It will take time to truly discover when and why COVID-19 causes gastrointestinal symptoms and how they affect disease severity and outcomes. And it will likely take much longer to figure out if and how often the symptoms become long-lasting.

But as daunting as it may sound, this knowledge could deliver significant improvements in the way we diagnose, treat, monitor, and track COVID-19.

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