COVID-19 pandemic has significantly changed lifestyles and cause stress worldwide. COVID-19 can affect post-recovery of gut function by resulting in underlying pathophysiological alterations, including dysbiosis, intestinal barrier disruption, intestinal inflammation, intestinal-pulmonary axis damage, immune dysregulation, and psychological stress [21]. However, only a few studies have reported the gastrointestinal sequelae of COVID-19 infection [21]. Besides, previous studies only studied IBS after COVID-19 infection, which only has a prevalence of 2.5%-5.3% [14, 17]. In the present study, IBS, and various FGIDs, such as FC, FD, and FDr, and their prevalence were investigated.
FGID is a brain-gut axis disorder whose pathogenesis is related to multiple factors, such as infection, psychosomatic factors, and gastrointestinal motility disorders [22]. However, the pathophysiological mechanism of prolonged and persistent GI symptoms during or even after COVID-19 infection is unclear. Previous studies detected RNA containing SARS-CoV-2 in the stool of 50% of patients during the period of infection, especially in patients with coexisting GI symptoms [23–24]. ACE2 receptor is highly expressed in the epithelial cells of the digestive tract [25], which establishes a pathway for SARS-CoV-2 to act in the GI tract. Structural components of SARS-CoV-2 contain stinging glycoproteins that bind to ACE2 receptors via membrane fusion, thus interfering with and suppressing host immune responses [26]. ACE2 receptor can attack host cells by binding to SARS-CoV-2, leading to tissue damage and inflammation. The target organ is also attacked to produce the corresponding clinical symptoms [27]. ACE2 also controls the intestinal expression of an amino acid transporter protein, B0AT1, which is involved in the tryptophan uptake. B0AT1 also maintains the tightness of intestinal connections and regulates mucosal cells involved in the defense barrier of the intestine [28]. SARS-CoV-2 can also cause impaired intestinal barrier function through ACE2, leading to elevated bacterial lipopolysaccharides and peptidoglycans, further promoting gastrointestinal inflammation [29]. In addition, the GI symptoms caused by SARS-CoV-2 infection may be associated with several factors, such as elevated 5-hydroxytryptamine (5-HT), dysbiosis of intestinal flora, and post-infection anxiety [29]. Some researchers found that most infected individuals continue to have dysbiosis of their intestinal flora long after recovery from COVID-19 [30]. A few studies also confirmed that intestinal microbiota can regulate the host immune response to SARS-CoV-2 infection and intestinal immune homeostasis [31].
In this study, the symptomatic patients were at greater risk of PI-FGID than asymptomatic infected patients. Diarrhea during the initial period of infection until long after the infection was the most common GI symptom among the infected patients, similar to the findings of physicians who studied the initial GI symptoms among infected patients in Wuhan, China [12]. A meta-analysis with 4243 SARS-CoV-2 infected patients revealed that severely symptomatic infected patients are more prone to have GI symptoms [32]. A study identified SARS-CoV-2 in the stool of 52.4% of infected patients who also had GI symptoms and in only the stool of only 39.1% of the infected patients without GI symptoms [24]. In this study, Rome III questionnaire results showed that the incidence of IBS was not significantly different between the post-COVID cohort and healthy controls. Nonetheless, these observations should be cautiously interpreted since the study had a small number of post-COVID-19 FGID patients.
Psychological stress can trigger FGID development [33]. Although antidepressants can be used to treat psychological stress, individual trials have shown variable results [34]. Anxiety can also predict the onset of FGID since about 23.65% of highly stressed stress individuals have at least one GI symptom, and about 31.1% of highly stress individuals have three or more GI symptoms during high stress [35]. In this study, anxiety or depression was not positively associated with the prevalence of post-COVID-19 FGID. PI-FGID, such as IBS and FD, are common among younger age groups [36]. Studies have also shown that the prevalence of PI-FGID is higher in women than in men [1, 36]. In this study, age and gender were not significantly associated with the prevalence of PI-FGID, and thus further studies are needed for verification.
Management options, including symptom-based treatment, have not been extensively explored in previous literature, probably due to the benign and self-resolving nature of PI-FGID. A recent research demonstrated that mast cell activation is one of the essential mechanisms of COVID-19 prolongation [37]. Therefore, H1/H2 blockers can improve symptoms in patients with extended COVID-19 [38].
However, this study has some limitations. First, the results are limited in representativeness due to the differences in gastrointestinal symptoms and severity exhibited by the different mutant strains of COVID-19 in different parts of the world. Second, the underlying mechanisms of post-COVID-19 FGID were not assessed.
In conclusion, COVID-19 individuals with GI symptoms may develop PI-FGID during the 6-month follow-up period.