COVID-19-induced gastrointestinal autonomic dysfunction: A systematic review

Table 5 Prevalence and underlying mechanism for common gastrointestinal autonomic dysfunction in patients with coronavirus disease 2019

Symptom(s)	Incidence	Underlying mechanism
Nausea and/or vomiting	Nausea: 1.0%-12.5%, vomiting 1.0%-27.5%	Release of neuroactive agents from enteroendocrine cells and inflammatory mediations → abdominal vagal nerve stimulation of dorsal medulla → projection of information to higher brain regions → nausea and vomiting
Diarrhea	2% and 50%	Targeting intestinal ACE2 by the virus → cytokine storms, increased intestinal barrier permeability, and gut dysbiosis → diarrhoea. Hepatic and pancreatic injuries may also cause diarrhea. Antibiotic-induced iatrogenic diarrhea caused by activating Clostridium spp. should also be considered
Anorexia	Up to 40%	Social pressure. Neuromodulation → miscommunication between brain-gut-adipose tissues → changes in brain serotonin and tryptophan concentrations → anorexia, anosmia, and related odor perception impairment → development and aggravation of anorexia
Abdominal pain	6.0% (vary depending on the population)	Inflammation-induced release of many cytokines and chemokines → activating pain-sensing neurons. ↑ Eosinophils → ↑eosinophil-derived neurotoxins → abdominal pain. Intestinal inflammatory infiltration → ↑ intestinal mucosal permeability and the direct effect of viruses can aggravate dysbiosis and cause changes in. Tryptophan metabolism → initiating peristaltic and secretory reflexes in the viscera and exacerbating inflammatory bowel disease symptoms, including abdominal pain. COVID-19 infection → ↓Na, K, Ca, and Mg → abdominal pain
Acid reflux	1.1%	Increased serotonin levels. Esophageal mucosal barrier damage caused by cytokine storms. Relaxation of the lower esophageal sphincter. Gastric and duodenal dysfunction leading to obstruction of gastric emptying
Gastrointestinal bleeding	1%-4.5%	Peptic and rectal ulcers. Impaired gastrointestinal mucosa integrity. Treatment-related (secondary bleeding)
Intestinal ischemia injury	Not well established	Venous thrombosis, pulmonary embolism, and mesenteric ischemia

ACE2: Angiotensin-converting enzyme 2; COVID-19: Coronavirus disease 2019.