key: cord-0806657-wt0gq4s8
authors: Jiang, Guiyuan; Cai, Yanping; Yi, Xue; Li, Yanping; Lin, Yong; Li, Qing; Xu, Jingqing; Ke, Mingyao; Xue, Keying
title: The impact of laryngopharyngeal reflux disease on 95 hospitalized patients with COVID‐19 in Wuhan, China: A retrospective study
date: 2020-06-02
journal: J Med Virol
DOI: 10.1002/jmv.25998
sha: 782ca995d5e53d6412b5844322e0c77f01e0db8e
doc_id: 806657
cord_uid: wt0gq4s8

Studies have demonstrated that comorbidities, especially cardiovascular and endocrine diseases, correlated with poorer clinical outcomes. However, the impact of digestive system diseases has not been issued. The aim of this study is to determine the impact of laryngopharyngeal reflux disease (LPRD) on hospitalized patients with coronavirus disease 2019 (COVID‐19). We extracted clinical data regarding 95 patients in Wuhan Jinyintan Hospital, Wuhan, China, between 26 January and 21 February 2020. The Reflux Symptom Index (RSI) was used to assess the presence and severity of LPRD. An RSI greater than 13 is considered to be abnormal. A total of 95 patients with COVID‐19 were enrolled, with 61.1% (58/95), 32.6% (31/95), and 6.3% (6/95) being moderately ill, severely ill, and critically ill, respectively. In this study, 38.9% (37/95) of the patient had an RSI score over 13, which was indicative of LPRD. In univariable analysis, the age and RSI scores of severely or critically ill patients were statistically significantly higher than patients with moderate disease (P = .026 and P = .005, respectively). After controlling for age difference in a multivariable model, the RSI greater than 13, compared to RSI equal to 0, was associated with significantly higher risk of severe infection (P < .001; odds ratio [OR] = 11.411; 95% confidence interval [CI], 2.95‐42.09) and critical infection (P = .028; OR= 19.61; 95% CI, 1.38‐277.99). Among hospitalized patients with COVID‐19, RSI scores greater than 13, indicative of LPRD, correlated with poorer clinical outcomes. The prevalence of LPRD may be higher than the general population, which indicated that COVID‐19 can impair the upper esophageal sphincter and aggravate reflux.

Since the outbreak of coronavirus disease 2019 in Wuhan, China, the disease, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is rapidly sweeping across the world. [1] [2] [3] The number of cases and the death toll of COVID-19 outside China has increased drastically involving 200 countries, states, or territories by 30 March 2020.

Although most of the confirmed cases presented with mild or moderate diseases, 13.8% and 4.7% were classified as severe and critically ill, respectively. 4 Previous studies demonstrated the existence of any comorbidity was associated with poorer clinical outcomes; and a greater number of comorbidities was also correlated with poorer outcomes. [5] [6] [7] [8] A meta-analysis to assess the prevalence of comorbidities in the patients with COVID-19 revealed that hypertension and diabetes were the most prevalent comorbidity, followed by cardiovascular diseases and respiratory system diseases. 5 However, the comorbidities in these studies were mostly determined based on self-report upon admission, which might result in missing data due to the patient's unawareness; and the impact of comorbid digestive system diseases among patients with COVID -19 have not been fully addressed. To further investigate the impact of gastrointestinal (GI) disorder, this study focused on the GI comorbidity, specifically, laryngopharyngeal reflux disease (LPRD).

According to the recent reports, the severity and clinical manifestations are quite heterogeneous at the time of diagnosis. 2, 7, 9, 10 The most common symptoms were fever and cough, whereas GI presentations were also found in a small number of patients. 2,11 Nausea or vomiting was reported in 5% of the cases, and diarrhea was found in 3.8% of the patients. 2 Also, studies have identified the SARS-CoV-2 RNA in the stool of infected patients, and angiotensin-converting enzyme 2 serving as the viral receptor was found to be highly expressed in GI tract, suggesting that the SARS-CoV-2 can infect the digestive system. 11-13 LPRD, a subtype of extraesophageal reflux, is a common disorder found in 5% of the people in China and 18.8% in Grace. 14, 15 The impairment of upper esophageal sphincter (UES) motility may aggravate the reflux of gastric contents beyond the esophagus into pharynx and larynx. On the basis of the fact that SARS-CoV-2 can infect the digestive system, we hypothesize that the virus may affect the GI motility and function, leading to repeated reflux of GI content into larynx may further facilitate the attack of the virus on the respiratory system. However, the prevalence and impact of LPRD in patients with COVID-19 have not been revealed in previous studies.

The Reflux Symptom Index (RSI) is a validated nine-item questionnaire for the assessment of the presence and severity of commonly reported symptoms, which proved to exhibit excellent construct and criterion-based validity. An RSI score higher than 13 is considered to be abnormal and indicative of LPRD. 16, 17 To address the issues mentioned above, the RSI was used in our study to evaluate the prevalence of LPRD in hospitalized patients with COVID-19 and assess the risk of LPRD in severe patients compared with non-severe patients.

A total of 95 patients with confirmed COVID-19 admitted to Wuhan Jinyintan Hospital, Wuhan, China, were enrolled in this study after receiving approval of the institutional review board between 26 January and 21 February 2020. The diagnosis criteria of COVID-19 in this study were based on the World Health Organization's interim guidance. 18 The epidemiological, clinical, laboratory, and radiological data were collected to determine the infection of SARS-CoV-2. Descriptions of chest X-ray or computed tomography (CT) were summarized by two separate radiological doctors. Patients whose real-time reversetranscription-polymerase chain reaction assay for nasal and pharyngeal swab was positive were confirmed with COVID-19.

All the patients were classified as being mildly, moderately, severely, or critically ill according to the Guidance for Corona Virus Disease 2019 (6th edition) released by the National Health Commission of China. 9, 19 Briefly, mildly ill denoted minimal symptoms and no findings of pneumonia on chest X-ray or CT; moderately ill is defined as the presence of symptoms including fever, cough, and so forth, and abnormal radiological findings;

severely ill denoted at least one of the following criterion (respiratory rate being 30 times per minute or greater, pulse oxygen saturation being 93% or lower, oxygen being 300 or lower, or rapid progression of pneumonia based on radiological findings in 24 to 48 hours); and critically ill denoted at least one of the criteria (septic shock requiring vasoactive medications, respiratory failure requiring mechanical ventilation, or other organ failure requiring intensive care unit admission).

The RSI was used to assess the presence and intensity of commonly reported LPRD symptoms. 16 The RSI score is from 0 to 5, with 5 being the worst, based on the severity of the following symptoms: hoarseness or a problem with your voice; clearing your throat; excess throat mucus or postnasal drip; difficulty swallowing food, liquids, or pills; coughing after you ate or after lying down; breathing difficulties or choking episodes; troublesome or annoying cough; sensations of something sticking in your throat or a lump in your throat; and heartburn, chest pain, indigestion, or stomach acid coming up. A score greater than 13 was considered to be clinically significant and indicative of LPRD. 16 This study aimed to reveal the correlation of LPRD or RSI with the severity of COVID-19.

The comparison between patients with different severity of COVID-19 was performed using univariate analysis, and a χ 2 test or a t test was used depending on the type of variable. Multivariate logistic regression was used to identify independent risk factors for COVID-19. All statistical analyses were plotted using SPSS 24.0 (IBM) and Origin 2019b (Origin Lab). 

The characteristics of patients who were moderately ill, severely ill, and critically ill were showed in Table 2 . In the univariable analysis, the frequency of males and females among the three groups showed no significant statistical difference (P = .907); however, the median age among the three groups demonstrated significant difference (P = .026). Meanwhile, the median RSI scores for the patient with moderate, severe, and critical diseases were 7, 13, and 14, respectively, which also showed a significant difference (P = .005). The difference of age and RSI scores among three groups was also demonstrated in Figure 1A ,B: severely and critically ill patients were significantly older than the moderately ill patients; the RSI scores of severely and critically ill were also significantly higher than that of the moderately ill patients. As a result, the age and RSI score may be risk factors for severely or critically ill patients. 

COVID-19 has become a global public emergency, resulting in thousands of deaths and affecting more than 1 million people 3 ; therefore, further understanding of the disease helps us to better contain the pandemic. In this study, we retrospectively analyzed the impact of LPRD, a common digestive disorder, on patients with COVID-19 and found that LPRD was commonly prevalent in hospi- which had more accuracy and validity than self-recalling. 16 We found that approximately 38.9% (37/95) of the hospitalized patients with COVID-19 had an RSI score greater than 13, which suggested that a large number of the patients might have comorbid LPRD. As a result, the prevalence of LPRD in patients may be higher than the general population based on the previous data. 14 A large study of 1099 patients from 522 hospitals reported nausea or vomiting in 55 (5.0%) and diarrhea in 42 (4.8%) patients.

The frequencies of diarrhea and vomiting varied among previous studies. 1, 2, 6, 9, 11 In a retrospective that collected data from A number of existing studies revealed that patients with comorbidities were more likely to have a severe infection and poorer clinical outcomes. 5, 8, 23 In addition to the most common comorbidities among patients with COVID-19 including circulatory and endocrine diseases, LPRD may be also associated with more severe disease. Our study demonstrated that both age and RSI scores of severely or critically ill patients were significantly higher than moderately ill patients. As with previous studies, older patients were more likely to develop the more severe or critical diseases. 6, 8, 9 In our study, patients with age ≥ 60 were 14 

Among hospitalized patients with COVID-19, RSI scores greater than 13, indicative of LPRD, correlated with poorer clinical outcomes. In addition, the prevalence of LPRD may be higher than the general population, which indicated that COVID-19 can, in turn, impair the UES and aggravate reflux. Assessment of LPRD using the RSI may help us with the risk stratification of patients upon admission.

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The impact of laryngopharyngeal reflux disease on 95 hospitalized patients with COVID-19 in Wuhan, China: A retrospective study

The authors would like to acknowledge all the patients and their families for their contributions to this study. No writing assistance was received.

The authors declare that there are no conflict of interests. 

http://orcid.org/0000-0001-8678-507X