Gastrointestinal symptoms of COVID-19: What we know and why it is important

GI symptoms associated with COVID-19

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

But early reports from China suggested that COVID-19 could also trigger GI symptoms. The GI system includes the:

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

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

The research is ever-evolving. According to a February 2021 review that included 125 articles and a total of 25,252 participants, the most common GI symptoms of COVID-19 included:

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

An earlier review, published in January 2021, found much broader rates of symptom prevalence, such as:

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

Less commonly, COVID-19 may also be associated with:

• belching
• acid reflux
• indigestion
• colitis, or intestinal inflammation
• GI bleeding

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

It seems that most people with GI symptoms of COVID-19 develop them alongside respiratory symptoms.

However, a review from late 2020 reported that 16% of people with SARS-CoV-2 infections only experienced GI symptoms. And sometimes, these symptoms developed before respiratory symptoms or a fever.

Early studies suggest that GI symptoms tend to occur in the early stages of the infection. And, according to a clinical update that appeared in The American Journal of Emergency Medicine in January 2022:

“[GI] symptoms are common, with up to one-third of patients with COVID-19 presenting first with GI symptoms. Nausea and vomiting may be present in up to two-thirds of patients with COVID-19. Approximately 40% of patients with COVID-19 will have loss of appetite, and up to 50% will have diarrhea. Abdominal pain is less common, occurring in less than 10%.”

How COVID-19 causes GI symptoms

Researchers are still learning 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 areas.

Studies show that SARS-CoV-2 enters intestinal cells 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 RNA. Like many viruses, SARS-CoV-2 carries its genetic information on a strand of RNA, 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.

Symptoms such as pain, nausea, and diarrhea may also occur if viruses damage GI tissues.

And research suggests that the composition of the gut microbiota, the community of microbes that inhabit the intestines or stomach, can influence COVID-19.

Once inside the GI tract, the virus can also travel through the portal vein, the vein that drains blood from the digestive tract. This process can allow viruses to affect the vagus nerve, causing nausea.

Meanwhile, nausea and diarrhea are common side effects of medications, such as antivirals, that healthcare professionals use to manage COVID-19.

Also, there is increasing evidence that SARS-CoV-2 could pass to others via fecal-oral transmission. This means that a person could acquire the 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 particles of SARS-CoV-2.

And research shows that people may shed viral particles in their feces after the virus is undetectable in the upper respiratory system, such as the lungs, nose, and throat.

This may change our understanding of how the virus can transmit to others and for how long.

GI symptoms and disease outcomes

People with GI symptoms of COVID-19 may be more likely to develop complications or be more at risk from those complications.

A study from November 2020 found that having GI symptoms was associated with a heightened risk of developing acute respiratory distress syndrome, as have subsequent studies.

The research also found that experiencing GI symptoms increased the likelihood of needing noninvasive mechanical ventilation and tracheal intubation, procedures that carry risks.

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

Another study, from December 2020, concluded that the presence of GI symptoms in adults was associated with more severe illness and fatal outcomes. A more recent review found that people with COVID-19 and GI symptoms on admission to the hospital were more likely to develop acute heart and kidney damage or die from the disease.

Studies have also suggested that people with preexisting GI conditions might experience more serious disease and negative complications.

Research published in February 2021 suggested people with GI conditions, such as Barrett’s esophagus, could have an increased risk of developing severe COVID-19.

Some researchers speculate that this connection may exist because GI diseases can cause intestinal metaplasia, which involves the stomach lining being replaced 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 inflammatory bowel disease, are associated with 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.

There has been less speculation about why having GI symptoms of COVID-19 seems to increase the risk of severe disease and poor outcomes in the absence of underlying health conditions.

People with viral infection in their respiratory and GI tracts may have been exposed to higher viral loads than people for whom the infection is limited to 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 affecting multiple organs also tend to experience more severe disease and poorer outcomes.

Early evidence seems generally consistent. But broader studies are needed to determine the true relationship between GI symptoms, GI conditions, and COVID-19.

For example, some research indicates that people who develop GI symptoms of 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 suggests, SARS-CoV-2 testing services could widen their reach to include people with appetite loss, vomiting, and diarrhea, with or without respiratory symptoms. This could help identify COVID-19 cases earlier.

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

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.

A similar study, published in January 2022, monitored global internet trends, and it concluded that internet search data could reliably predict “COVID-19 outbreaks at both global and regional levels.”

Researchers also need to know whether having a preexisting GI disease increases the risk of severe COVID-19, complications, and death. And they will have to figure out whether GI conditions make people more prone to developing COVID-19.

This could help healthcare professionals know how to handle potential, active, or resolved cases of COVID-19 in people with GI diseases better.

It will also be important to confirm whether COVID-19 can spread through feces, and if so, how long this is possible.

In a review from early February 2021, 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) recommend that people self-isolate for 5–20 days after the onset of COVID-19 symptoms, depending on specific symptoms and their severity. If feces can spread the infection for longer, and this mode of transmission is a cause for concern, public health bodies may have to review 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.

Meanwhile, researchers also need to learn more about the long-term effects of COVID-19 on the GI tract.

Some preliminary studies show that certain symptoms may persist for weeks or months after the person has recovered from the initial illness. A recent review found that 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 fully understand when and why COVID-19 triggers GI symptoms and how they affect disease severity and outcomes. For now, as a meta-analysis published in February 2022 concluded, it seems that GI symptoms and abdominal pain are associated with more severe disease.

It will likely take even longer to figure out whether and how often symptoms persist.

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

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.