Learning design

This prospective cohort study was conducted in adults between July 2022 and February 2023. At the time of the study, China was undergoing a severe outbreak of COVID-19, which Omicron ruled [14, 15], a variant of SARS-CoV-2, and all people were screened for COVID everywhere in the hospital or in the community with a standard universal reverse transcription polymerase chain reaction (RT-PCR) test. All suspected COVID individuals, even due to asymptomatic infection, were referred to local hospitals or large rectangular cabin hospitals for mandatory quarantine. All suspected infected individuals who underwent a diagnostic procedure, such as a nasopharyngeal polymerase chain reaction (PCR) or a chest X-ray to show their lung involvement, had a definite diagnosis of coronavirus infection by their physician. Patients with COVID−19 are included in the study according to inclusion or exclusion criteria as soon as a diagnosis of COVID−19 is confirmed. Gastrointestinal work was required, including biopsies, blood samples (CBC, WBC count, CPR, PCT, IL−6, IgG and IgM antibody tests for viruses) and other tests (x-rays and ultrasound, urinalysis, stool) to rule out other bacteria – and viral infections of the whole body or part of the body or acute gastroenteritis (AG) that could cause gastrointestinal symptoms. The delay from diagnosis of COVID-19 to participation in the study is no more than 1 day. All patients received the national protocol of standard treatment without modification.

It consisted of 2 cohorts, a case group that included consecutively recruited COVID-19 patients from Fangcai Hospital, a dedicated COVID care center, in Haikou, Hainan Province, China. A healthy control group included negative screening at our hospital at the same time for COVID serology. Participants were followed up either physically in an outpatient setting or by telephone at 1, 3, and 6 months using a validated Rome III and Rome IV questionnaire and limited objective assessments. [1]. The follow-up period from July-August 2022 to February 2023 was more than 6 months. The data from case groups were compared with 6-month follow-up data on the development of FGID in a group of healthy subjects matched for age and sex. In addition, individuals who met the various diagnostic criteria for FGID in Rome at the 6-month follow-up were advised to come to the clinic for further examination with laboratory and endoscopy methods as well as clinical indications to rule out some diseases such as gastritis, SIBO, microscopic colitis, etc. Clinical indicators include duration and frequency of diarrhea, stool consistency and presence of blood, history of vomiting, fever, abdominal cramping, and weight loss. Enrolled COVID-19 patients and healthy controls were tested for COVID-19 at 3 and 6 months to rule out COVID-19 reinfection. The questionnaires also included comorbidities (hypertension or diabetes), anxiety, irregular diet, sleep quality and regular exercise.

Case group inclusion criteria were as follows: (1) age between 18 and 85 years, with a final diagnosis of coronavirus of varying severity [16, 17] (mild and moderate) using biochemical test data (such as COVID19-SARS-CoV-2 positive and anti-SARS-CoV-19 IgG and IgM negative) or chest CT and observation of lung involvement; (2) no previous a history of clinical confirmation of the diagnosis of any FGID, no gastrointestinal neoplasm, reflux esophagitis, ulcerative colitis, or other gastrointestinal disease, no comorbidities (hypertension or diabetes), no history of abdominal surgery, and no recurrent baseline FGID or gastrointestinal symptoms such as diarrhea, constipation, or abdominal pain; (3) blood samples and other tests were necessary to rule out AG, bacterial and viral infections; (4) normal results of gastroscopy and other laboratory tests from the last 6 months of medical examination were required. A healthy control group had no history of COVID-19 or FGID. Biochemical test data (such as COVID19-SARS-CoV-2 negative and anti-SARS-CoV-19 IgG and IgM negative) are required, and the rest of the criteria were the same as for the case group.

The objectives of this study were explained in detail to all participants and also participation in this study was fully conscious and based on their desire. Furthermore, written informed consent was obtained from each participant. At the same time, each participant provided written or electronic informed consent, and the study was approved by the Institutional Ethics Committee of the Second Hospital of Hainan Medical University (reference number: LW2022270).


RT-PCR was used to detect SARS-CoV-2 in nasopharyngeal and oropharyngeal samples of individuals [18]. The diagnosis of IBS according to the Rome IV diagnostic criteria has changed significantly, the new diagnostic criteria have increased the frequency required to diagnose IBS and the frequency of IBS has decreased [1]. We used Rome III rather than the recently described Rome IV criteria as the latter is 50% less sensitive for the diagnosis of IBS [1]. Other types of FGID were diagnosed based on the Rome IV criteria [1].

Dyspepsia refers to postprandial discomfort syndrome, which often manifests as postprandial fullness and early satiety (inability to finish a normal meal). Dyspepsia means the same as Functional dyspepsia and refers only to post-meal discomfort syndrome.

AG was defined as the presence of at least two of the following: (i) diarrhea, (ii) vomiting, (iii) fever, and (iv) a stool culture isolating intestinal disease. [6]. A stool sample from each COVID-19 patient was examined under a microscope to detect pus cells, erythrocytes or parasites. All suspected stool specimens were cultured for Vibrio cholerae, Salmonella, Shigella, Campylobacter, and Aeromonas using standard techniques to identify pathogenic strains.

Patients who showed signs of organ failure (such as persistent ischemia, severe respiratory distress) or required ventilatory support or intensive care unit admission during treatment for a COVID-19 infection were defined as having severe COVID-19. Severity of COVID-19 [16, 17, 19] was graded as described: (i) severe (required ventilator), (ii) severe (required oxygen), (iii) moderate (although pneumonia was present, did not require oxygen) and (iv) mild (only symptoms from upper respiratory system). Those who were asymptomatic at diagnosis of COVID-19 were classified as asymptomatic as categorical variables (yes or no).

Living with frequent (> 5 times/month) infrequent meals and irregular meals was defined as disordered eating. Pittsburgh Sleep Quality Index (PSQI) [20] was used to examine patients’ sleep quality. The PSQI total score ranges from 0 to 21, with 7 being the threshold for sleep quality problems, and a higher score above 7 indicating poorer sleep quality for the patients, while the opposite indicates better sleep quality for the patients. Regular physical activity is defined by the latest World Health Organization (WHO) Physical Activity and Sedentary Guidelines 2020 [21]. Adults should do at least 150–300 minutes of moderate-intensity aerobic exercise per week, or at least 75–150 minutes of vigorous aerobic exercise, or an equivalent combination of moderate and vigorous exercise; Older adults should engage in at least 150–300 minutes of moderate-intensity aerobic exercise per week, or at least 75–150 minutes of vigorous-intensity aerobic exercise, or an equivalent combination of moderate and vigorous exercise. Hamilton Anxiety Scale [22] was used to assess the psychological status of the case group, and possible anxiety was considered when the scale was > 7.

statistical analysis

Calculation of sample size

In this study, the sample size was calculated as 90% power, 99% confidence interval (two-sided) based on previous studies [12, 23, 24] which showed that the average frequency of FGIDs after acute gastroenteritis is about 21% and a Chinese study that showed the frequency of PI-FGIDs in a control group of 8.2% [25]. A total of 155 COVID-19 patients and 155 healthy controls were required in this study, but 194 COVID-19 patients and 194 controls were enrolled, with a potential loss to follow-up of 10–20%. Four of 194 COVID-19 patients and 34 of 194 healthy controls were excluded because they had insufficient documentation or were lost to follow-up. Finally, 190 COVID-19 patients and 160 healthy controls were analyzed (Figure 1).

Figure 1
figure 1

Data collection and analysis

SPSS (version 26; SPSS Inc, Chicago, IL) was used for all statistical analyses. Categorical data were presented as proportions, while continuous data were presented as mean ± standard deviation (SD) or median and range or interquartile range (IQR). Categorical variables were analyzed by χ2 test with Yates correction, where appropriate. Parametric and nonparametric continuous data were analyzed using unpaired t-test and Mann-Whitney U test, respectively. Multivariate analysis was performed using stepwise logistic regression. A two-sided P value < 0.05 was considered significant.

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