The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the virus responsible for the coronavirus disease 2019 (COVID-19), has infected over 219 million worldwide and caused the deaths of almost 4.55 million.
The SARS-CoV-2 virus can result in massive inflammation in the gastrointestinal (GI) tract of infected individuals, which can lead to several clinical symptoms including diarrhea. Previous reports have found that diarrhea prior to COVID-19 infection or COVID-19-induced diarrhea often increases the risk of a poor prognosis.
Previous studies have found that flavonoids can help prevent diarrhea. Flavonoids are a type of phytochemical found in certain foods like berries, kale, onions, and red cabbage. A recent study published in Tropical Biomedicine determines whether flavonoids can help prevent diarrhea caused by SARS-CoV-2 infection.
The researchers found that flavonoids can help prevent diarrhea in COVID-19 patients when used in conjunction with vitamin D. This combination treatment can activate nuclear factor erythroid-derived-2-related factor 2 (Nrf2 transcription factor), which downregulates the expression of the angiotensin-converting enzyme 2 (ACE2) receptor in cells.
Diarrhea in COVID-19
While COVID-19 is primarily a respiratory illness, individuals with COVID-19 can experience many other symptoms as well. Diarrhea is a common clinical symptom in COVID-19 patients.
Diarrhea was also a common symptom in SARS in 2003, and it is a symptom in the Middle East respiratory syndrome known as MERS. Both are similar to SARS-CoV-2. Approximately 11% of patients with an acute SARS-CoV-2 infection will also have diarrhea.
Once the SARS-CoV-2 virus enters a body, it triggers the immune system to prevent the replication of the virus. Initially, SARS-CoV-2 infects the human lungs after binding with the ACE2 receptor, which subsequently causes the body to increase the levels of angiotensin II in the blood. As a result, the body releases chemokines, as well as activates cytotoxic (CD8+) and helper (CD4+) T-cell lymphocytes, macrophages, and natural killer (NK) cells.
Cytotoxic T-cells produce interleukin-2 (IL-2) and interferon-gamma (IFNγ), whereas the helper T-cells release pro-inflammatory cytokines like the IL-4, IL-17, IL-21, and IFNγ. Taken together, these substances cause a massive release of mucus that may lead to severe acute respiratory distress syndrome.
When there are higher levels of cytokines in the blood, the gut may also be affected. The inflammation may cause considerable damage in the layers of the intestinal mucosa. In addition, an imbalance in the gut microbiome (dysbiosis) and damage to the mucosal cellular barriers enable SARS-CoV-2 multiplication and transmission to other areas in the body. It is this dysbiosis that causes diarrhea, stomach pain, blood in the stool, and mucus secretions.
Role of Flavonoids Against SARS-CoV-2 Induced Diarrhea
Flavonoids are commonly found in plants and vegetables. Some of the most common flavonoids include quercetin, baicalin, hesperidin, luteolin, gallocatechol, and epigallocatechin, all of which are secondary metabolites of plants. They are antioxidant, anti-inflammatory, and antimicrobial agents.
Flavonoids can also help boost the immune system’s ability to fight infections by inhibiting some enzymes that are important for the SARS-CoV-2 replication.
In the current study, the researchers found that flavonoids, particularly epigallocatechin-3-gallate found in green tea, along with vitamin D3, can activate the Nrf2 transcription factor. The activation of the Nrf2 transcription factor subsequently downregulates ACE2 expression from the cellular surfaces.
Flavonoids also have the potential to alleviate COVID-19 and/or ease diarrhea. Quercetin, the most popular flavonoid, has been shown to prevent the interaction of the SARS-CoV-2 spike protein and ACE2 receptor and suppress the inflammatory markers.
The exact role of flavonoids against COVID-19-induced diarrhea is still preliminary and needs more research. As a result, there remains a need for preclinical and clinical studies to further explore the full potential of these compounds against COVID-19-induced diarrhea.