COVID-19 is primarily a respiratory illness, but a significant number of people experience gastrointestinal symptoms, with diarrhea being a common complaint. Studies suggest that between 10% and 20% of patients with COVID-19 report diarrhea, which can sometimes be associated with a more severe course of the disease. This intestinal distress results from the virus interacting directly and indirectly with the digestive tract. The mechanisms involve the virus’s entry strategy, cellular destruction, the body’s inflammatory response, and alterations to the gut’s microbial ecosystem.
How SARS-CoV-2 Targets the Digestive System
The SARS-CoV-2 virus enters human cells by binding to a specific protein on the cell surface called the Angiotensin-converting enzyme 2 (ACE2) receptor. This receptor acts like a docking station the virus uses to gain entry. While ACE2 is highly concentrated in the lungs, it is also abundantly expressed on cells throughout the digestive system.
The cells lining the small and large intestines, known as enterocytes, possess a high density of ACE2 receptors. This makes the gut a highly susceptible target for viral entry and replication. The virus also uses a host enzyme called TMPRSS2, which is co-expressed with ACE2 in the gut and helps cleave the viral spike protein, facilitating the entry process.
Direct Viral Damage to Intestinal Cells
Once SARS-CoV-2 enters the enterocytes, it begins to replicate, leading to direct cellular damage and death. Viral genetic material and proteins have been detected in the intestinal epithelial cells of COVID-19 patients, suggesting the virus actively infects the gut lining. This direct viral attack causes the premature death of enterocytes, which can lead to the sloughing of the intestinal lining.
The damage compromises the integrity of the intestinal barrier, which normally absorbs water and nutrients. When these absorptive cells are destroyed or impaired, the intestine loses its ability to pull water back from the fecal matter. This failure in water reabsorption, combined with the activation of ion channels that promote fluid secretion into the bowel, results in an excess of fluid in the colon. This malabsorption and increased fluid secretion is the direct cause of the loose, watery stools characteristic of diarrhea.
The Impact of Systemic Inflammation
Beyond the direct damage caused by the virus, the body’s systemic immune response contributes significantly to gastrointestinal distress. This response involves the release of pro-inflammatory signaling molecules, such as cytokines, into the bloodstream. These cytokines travel through the circulation to affect distant organs, including the intestines.
The surge of inflammatory mediators increases the intestinal lining’s permeability, sometimes referred to as a “leaky gut.” This allows substances within the bowel to pass into the underlying tissue, triggering further local inflammation. The inflammatory molecules also interfere with the function of cells that regulate water and ion movement, promoting fluid secretion. This inflammatory state can also stimulate the enteric nervous system, leading to hyper-motility, where the intestine contracts too quickly, rushing contents through the digestive tract.
Disruption of the Gut Microbiome
The final contributing factor to COVID-19-related diarrhea is the disruption of the gut microbiome, the community of bacteria and other microbes living in the intestines. This imbalance, known as dysbiosis, is caused by the viral presence, inflammation, and sometimes by antibiotics administered for secondary bacterial infections. Patients with COVID-19 often have a decreased abundance of beneficial bacteria, such as those that produce short-chain fatty acids important for gut health.
Conversely, there can be an increase in pathogenic bacteria, shifting the microbial balance toward a less healthy profile. This altered ecosystem impairs the gut’s normal functions, including maintaining a healthy barrier and regulating digestion. Dysbiosis can perpetuate inflammation and may be responsible for the persistence of gastrointestinal symptoms, even after the virus has been cleared. Diarrhea in COVID-19 results from this combination of direct viral destruction, systemic immune response damage, and ecological disruption of the gut’s microbial community.