A prospective study of extraesophageal reflux and potential microaspiration in patients hospitalized with COVID-19 in Jordan

Abstract

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lung infection has represented a global challenge. Intriguingly, it has been shown that the alveolar lung epithelium expresses little Angiotensin Converting Enzyme receptor protein (ACE2), the entry receptor for SARS-CoV-2. Upper airway establishment of infection and translocation to the lung is well documented but other anatomical niches may be relevant to potentially serious lung infection. ACE2 is heavily expressed in the gastrointestinal tract and gastrointestinal symptoms support a clinical diagnosis of Coronavirus disease 2019 (COVID-19). This suggests a research question and the need to gather patient data exploring potential aerodigestive links in SARS-CoV-2 tranlocation and infection which may be relevant in the peripheral lung. This recognizes anatomical proximity and concepts of bi-directional movement between the Gastrointestinal and lung systems in normal physiology and disease. We have therefore explored the potential for gastro oesophageal reflux disease (GORD) micro aspiration and aeorodigestive pathophysiology in a novel prospective investigation of patients hospitalized with COVID-19. Methods This is a prospective descriptive cohort study of 210 patients who were hospitalized with a confirmed diagnosis of COVID-19. The cohort was divided into three groups of patients based on symptom severity and radiological results. The Reflux Symptom Index (RSI) was used to evaluate the presence and severity of GOR. An RSI greater than 13 is considered to be abnormal. Patients’ saliva samples were tested using enzyme-linked immunosorbent assay (ELISA) to determine the level of salivary pepsin among the cohort of patients. Results A total of 210 patients with COVID-19 were enrolled in the study with 55.2% (116/210) classified as mildly ill, 31.9% (67/210) moderately ill and 12.9% (27/210) as severely ill. 34% (72/210) of the patients had an RSI score of over 13 and a median salivary pepsin value of 54 ± 29 ng/ml which suggested an incidence of extraesophageal reflux (EOR) in around a third of patients. The presence of respiratory comorbid conditions, an RSI score of over 13 and a salivary pepsin level of > 76ng/ml increased the risk of developing a more severe COVID-19 infection. Conclusion The study showed a high prevalence of EOR among the study cohort and provide the first prospective evidence suggesting the potential for aerodigestive pathophysiology including microaspiration in COVID-19 disease. We believe that the results of our study support the need for more extensive research.

Critical appraisal of how COVID-19 infection and imposed lockdowns have impacted gastroesophageal reflux: A review

“…There is only 1 existing study that has examined the prevalence of EER in patients hospitalized due to COVID-19 and the impacts that EER has on the severity of COVID-19 infection. [ 89 ] Al-Momani, Mashal, Al Balawi, Almasri, AL-Shudifat, Khasawneh, Pearson and Ward [ 89 ] employed the reflux symptom index to evaluate the incidence of EER as well salivary pepsin levels were measured to serve as a reliable marker for EER. [ 90 ] Al-Momani, Mashal, Al Balawi, Almasri, AL-Shudifat, Khasawneh, Pearson and Ward [ 89 ] showed that respiratory comorbidity, salivary pepsin level, and reflux symptom index score are risk factors for a patient development of a more severe COVID-19 illness.…”

“…[ 89 ] Al-Momani, Mashal, Al Balawi, Almasri, AL-Shudifat, Khasawneh, Pearson and Ward [ 89 ] employed the reflux symptom index to evaluate the incidence of EER as well salivary pepsin levels were measured to serve as a reliable marker for EER. [ 90 ] Al-Momani, Mashal, Al Balawi, Almasri, AL-Shudifat, Khasawneh, Pearson and Ward [ 89 ] showed that respiratory comorbidity, salivary pepsin level, and reflux symptom index score are risk factors for a patient development of a more severe COVID-19 illness. The findings of this study thus add significantly to the body of knowledge currently available regarding the effects of EER, a prevalent GI condition, on individuals with COVID-19.…”