COVID-19 Is Able To Cause Gastric Reflux

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Gastric Reflux – COVID-19: In the last 18 months, physicians and also entities involved with gastric reflux education and care for patients in the UK and the United States have been struck by the number of patients that who describe the sudden onset of reflux type symptoms.

Besides the typical heartburn esophageal type symptoms, other more commonly symptoms reported included laryngo-pharyngeal (LPR) problems including a sore throat, throat clearing, globus and dysphonia (husky voice).
 
Many times, the onset of these symptoms coincided with a positive PCR test and a diagnosis of COVID-19, sometimes with other symptoms which may or not have been a manifestation of COVID and sometimes in isolation, with patients otherwise remaining entirely well.
 
In one case report published in the American Journal of Gastroenterology, a patient developed symptoms of heartburn after anti-reflux surgery without evidence of surgical complications or improvement with medications. The timing of both exposure to SARS-CoV-2 and symptom onset was helpful in making a diagnosis of COVID-19 associated esophageal hypersensitivity. https://journals.lww.com/ajg/fulltext/2020/10001/s2041_covid_19_associated_with_esophageal.2041.aspx

The definition of gastrointestinal involvement in post-acute COVID-19 syndrome, its frequency and its pathophysiology are still not completely understood. … https://www.nature.com/articles/s41575-022-00611-z

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) have been associated with approximately 447 million cases and 6 million deaths worldwide. In a subset of convalescent individuals, long-term sequelae termed ‘long COVID’, or ‘post-acute COVID-19 syndrome’ (PACS) are increasingly reported, with the most common manifestations being systemic, neuropsychiatric, cardio-respiratory and gastrointestinal1.

Owing to the robust constitutive expression of angiotensin-converting enzyme 2 on the brush border of the small intestinal mucosa, acute COVID-19 is associated with gastrointestinal symptoms such as nausea, vomiting, diarrhoea and abdominal pain1. In patients with PACS, gastrointestinal-related symptomatology includes loss of appetite, nausea, weight loss, abdominal pain, heartburn, dysphagia, altered bowel motility and irritable bowel syndrome1.

The frequency of PACS gastrointestinal symptoms is still not clearly defined. In a prospective cohort of 1,783 COVID-19 survivors (with 749 responders to survey questionnaires), 220 patients (29%) self-reported gastrointestinal symptoms at 6 months that included diarrhoea (10%), constipation (11%), abdominal pain (9%), nausea and/or vomiting (7%) and heartburn (16%)2.

In a different study of 73,435 users of the Veterans Health Administration, motility disorders (including constipation and diarrhoea), oesophageal disorders, dysphagia and abdominal pain were reported3. Laboratory abnormalities included an increased risk of high incident serum levels of alanine aminotransferase3.

Emerging evidence demonstrates persistent and aberrant inflammation as well as induction of autoimmunity in a subset of patients with PACS1 (Fig. 1). Viral persistence beyond acute COVID-19 has also been documented within multiple organs, including the gastrointestinal tract and central nervous system1. However, conclusive evidence linking viral persistence to PACS has not been demonstrated thus far.

figure 1
The external blue circle represents proposed pathophysiological mechanisms in post-acute COVID-19 syndrome (PACS). The internal grey circle represents gastrointestinal-PACS-specific pathophysiological mechanisms. ITP, idiopathic thrombocytopenic purpura.

 
The incidence of gastric reflux though not common at that time, was already reported during the early days of the COVID-19 pandemic in China. https://gut.bmj.com/content/69/6/997
 
Interesting, it is not suspected that some of the new emerging BA.2 subvariants like the BA.2.12 and more so the BA.2.3 and BA.2.3.4 subvariants are exhibiting a tropism towards the gastrointestinal tract and causing a variety of gut issues including acid reflux.

In Alberta, Canada, where these variants are rampant, media reports are already showing an increase in gastrointestinal issues. https://globalnews.ca/news/8800394/alberta-covid-19-gastro-symptoms/

A study published last year found that 60% of patients presenting for anti-reflux surgery have Small Intestinal Bacterial Overgrowth (SIBO). This condition is associated with the use of PPIs and anti-biotics as well as disrupted gastrointestinal motility. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8599257/

Whether COVID causes intestinal neurological injury is unknown but certainly gastrointestinal symptoms are well described in COVID and the gut is rich in angiotensin receptors. Fermentation by micro-organisms of sugars within the small bowel, which is usually relatively sterile, causes release of intra-luminal gas and consequent excessive belching.

This belching of aerosolized gastric contents into the esophagus and throat is thought to cause reflux symptoms.

Already many studies have shown that SARS-CoV-2 causes gut microbiome dysbiosis.
https://www.frontiersin.org/articles/10.3389/fmed.2022.821777/full
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198029/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402052/
https://www.sciencedirect.com/science/article/pii/S0753332220311392
https://gut.bmj.com/content/71/3/544
https://www.biorxiv.org/content/10.1101/2021.07.15.452246v1
https://www.biocodexmicrobiotainstitute.com/en/pro/gut-dysbiosis-sars-cov-2-infected-monkeys
Such gut microbiome dysbiosis can also trigger gastric reflux.

A Harvard Gastric Reflux – COVID-19 study has also confirmed that gastric reflux manifestations are a growing gastrointestinal issue in many Post-COVID-19 patients. https://scholar.harvard.edu/cvt/covid-long-haulers-gastrointestinal-system%C2%A0

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