Abstract
Gastrointestinal (GI) symptoms are highly prevalent in coronavirus disease 2019 (COVID-19) ranging from 17.6 % to 53 %.1–4 The proposed mechanism for GI symptoms involves SARS-CoV-2 virus binding to the host cell's angiotensin-converting enzyme-2 receptor, commonly found in GI tract epithelial cells.5
Gastrointestinal (GI) symptoms are highly prevalent in coronavirus disease 2019 (COVID-19) ranging from 17.6 % to 53 %.1, 2, 3, 4 The proposed mechanism for GI symptoms involves SARS-CoV-2 virus binding to the host cell's angiotensin-converting enzyme-2 receptor, commonly found in GI tract epithelial cells.5
With an increasing population of patients recovering from acute infection, there is now interest in understanding post-COVID-19 sequelae. Our study aims to report GI sequelae 3 and 6 months after hospitalization for COVID-19 infection.
Methods
This is a multicenter, retrospective study of hospitalized adult patients (18 years and older) who tested positive for COVID-19 infection from March 1, 2020 to January 24, 2021 across 12 hospitals comprising the Northwell Health System in New York. Patients were included if they (1) tested positive for SARS-CoV-2 nasal swab polymerase chain reaction, (2) were hospitalized with GI manifestations on initial presentation, and (3) had 3 and/or 6 months follow-up as an outpatient posthospitalization or repeat hospitalization. Further description of methods is included in the Supplementary Methods.
Results
During the study period, 17,462 COVID-19 patients were hospitalized. Of the 17,462 patients, 3229 (18.5 %) also had GI manifestations. A total of 715 (22.1 %) patients had 788 (24.4 %) distinct GI manifestations and also had 3- and/or 6-months outpatient follow-up data post-discharge. Patient characteristics are shown in Table 1 .
Table 1.
Results Summary of Patients With COVID-19 Infection With GI Symptoms at 3- and/or 6-Month Follow-Up
| Patient demographics | Median (IQR) or n (%) |
|---|---|
| Patients (+) COVID-19, n | 17,462 |
| Patients with GI symptoms, n (%) | 3229 (18.5) |
| Patients with GI symptoms + follow-up, n (%) | 715 (22.1) |
| Distinct GI symptoms in patients | 788 (24.4) |
| Patients with 3-mo follow-up, n (%) | 627 (88.7) |
| Patients with 6-mo follow-up, n (%) | 404 (56.5) |
| Median age, y (IQR) | 66 (IQR, 55 to 76) |
| Female, n (%) | 336 (46.9) |
| Race/ethnicity, n (%) | |
| White | 325 (46) |
| African American | 161 (23) |
| Hispanic | 121 (17) |
| Asian | 50 (7) |
| Native American, Alaskan, Hawaiian | 5 (0.5) |
| Length of stay, d (IQR) | 9 (5 to 17) |
| Mechanical ventilation | 101 (14.1) |
| BIPAP | 36 (5.0) |
| Vasopressors | 106 (14.8) |
| Irritable bowel syndrome | 7 (1.0) |
| Inflammatory bowel disease | 14 (2.0) |
| GI symptoms | |
| Gastroenteritis, n (%) | 414 (52.5) |
| Resolution at 3 mo | 323 (90.5) |
| Resolution at 6 mo | 210 (89.5) |
| GI bleeding, n (%) | 161 (20.4) |
| Resolution at 3 mo | 138 (92.0) |
| Resolution at 6 mo | 89 (94.7) |
| Malnutrition, n (%) | 181 (23.0) |
| Present at 3 mo | 81 (53.6) |
| Present at 6 mo | 33 (32.4) |
| Pancreatitis, n (%) | 4 (0.5) |
| Resolution at 3 mo | 4 (100) |
| Resolution at 6 mo | 4 (100) |
| Endoscopy for GI bleeding | |
| Underwent endoscopy | 19 (11.8) |
| Upper endoscopy | 15 (9.3) |
| Lower endoscopy | 4 (2.5) |
| Underwent intervention | 4 (2.5) |
| Findings | |
| Gastric and duodenal ulcers | 4 (21.1) |
| Gastritis, duodenitis | 4 (21.1) |
| Angioectasias | 3 (15.8) |
| Rectosigmoid ulcers | 1 (5.3) |
| Diverticulosis | 1 (5.3) |
| Hemorrhoids | 2 (10.5) |
| Normal | 4 (21.1) |
| Weight measurements | |
| Median weight on admission, lb (IQR) | 156.4 (131.7 to 193) |
| Median weight loss 3 mo, lb (IQR) | -4.9 (-16.7 to +6.6) |
| Median weight loss 6 mo, lb (IQR) | -2.2 (-19.6 to 11.8) |
| Patients unable to gain weight | |
| 3 mo, n (%) | 81 (59.1) |
| 6 mo, n (%) | 44 (56.4) |
| Median weight loss 3 mo, lb (IQR) | -14.7 (-26.6 to -7.9) |
| Median weight loss 6 mo, lb (IQR) | -17.8 (-35.2 to -6.5) |
| Patients with malnutrition | |
| Malnutrition + mechanical ventilation | 36 (19.9) |
| Malnutrition + BIPAP | 11 (6.1) |
| Malnutrition + vasopressors | 41 (22.7) |
BIPAP, bilevel positive airway pressure; GI, gastrointestinal; IQR, interquartile range.
Initial GI symptoms were as follows: gastroenteritis in 414 (52.5 %), GI bleeding in 161 (20.4 %), malnutrition in 181 (23.0 %), and idiopathic pancreatitis in 4 (0.5 %) patients. Gastroenteritis resolved in 323 (90.5 %) patients at 3 months and 210 (89.4 %) at 6 months. GI bleeding resolved in 138 (92.0 %) patients at 3 months and 89 (94.7 %) at 6 months. Malnutrition remains in 81 (53.6 %) patients at 3 months and 33 (32.4 %) at 6 months. Pancreatitis attributed to a viral etiology resolved in all patients at 3 months and 6 months.
For patients with malnutrition, median weight on admission was 156.4 pounds (interquartile range [IQR], 131.7–193.0). Median weight loss for patients at 3 months was -4.9 pounds (IQR, -16.7 to +6.6) and at 6 months -2.2 pounds (IQR, -19.6 to 11.8), respectively. Interestingly, 81 (59.1 %) patients were unable to gain weight at 3 months and 44 (56.4 %) were unable to gain weight at 6 months. For patients with malnutrition unable to gain weight at follow-up, median weight loss was -14.7 pounds (IQR, -26.6 to -7.9) at 3 months and -17.8 pounds (IQR, -35.2 to -6.5) at 6 months.
Discussion
We report the following important findings from 3- and 6-month follow-up regarding GI symptoms and COVID-19 disease:
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GI manifestations of COVID-19 disease are common (18.5 % in our cohort).
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Most initial presentations of GI bleeding, gastroenteritis, and pancreatitis associated with COVID-19 infection resolve by 3-months follow-up.
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Malnutrition is the most persistent GI sequelae without resolution at 3- and 6-months follow-up intervals. A significant portion of patients with these complaints may have difficulty gaining weight long term (ie, a median 17.8-pound weight loss remained for these patients at 6-months follow-up).
Our study provides reassurance that most individuals with the onset of GI bleeding or gastroenteritis associated with COVID-19 infection will have resolution of these symptoms. Our study highlights the need to pay particular attention to COVID-19 patients who suffer from malnutrition during their initial hospitalization. Many of these patients may have ongoing malnutrition or weight loss despite resolution of COVID-19 infection. Therefore, it may be imperative to establish malnutrition screening practices in post-COVID 19 patients who have recovered from acute infection.6 , 7
The strengths of our study include the largest cohort of patients with follow-up data of COVID-19-associated GI symptoms to date; a diverse patient population across multiple hospitals in Long Island, Manhattan, Queens, and Staten Island making results more generalizable; and manual chart review to confirm GI findings on admission and follow-up visits. Moreover, patients were diagnosed with malnutrition by a dedicated nutrition service. Limitations of our study lie inherently in the retrospective design. Other considerations include our follow-up data being restricted to our network facilities (although they are quite expansive spanning across Long Island and New York City) and 6-month follow-up is not yet available for several patients who developed COVID-19 infection later in the study interval.
In conclusion, GI symptoms of malnutrition, weight loss, and anorexia may persist for several months after COVID-19 infection and may require further medical attention, whereas GI bleeding, gastroenteritis, and pancreatitis are likely to resolve after initial presentation.
Footnotes
Conflicts of interest This author discloses the following: Arvind J. Trindade is a Consultant for Pentax Medical. The remaining authors disclose no conflicts.
Note: To access the supplementary material accompanying this article, visit the online version of Clinical Gastroenterology and Hepatology at www.cghjournal.org, and at http://doi.org/10.1016/j.cgh.2012.11.00
Supplementary Methods
Institutional review board approval was obtained for this study. International Classification of Diseases-10 codes for the following gastrointestinal symptoms were used to screen patients for initial GI manifestations: gastrointestinal bleeding (upper GI bleed, lower GI bleed, melena, hematochezia, hematemesis, bright red blood per rectum), gastroenteritis (abdominal pain/diarrhea/nausea/vomiting), malnutrition (including severe, moderate, mild protein calorie malnutrition per nutrition assessments, and anorexia), and pancreatitis. These GI manifestations were selected for the following reasons: gastroenteritis symptoms have been well described as a component of the acute presentation of COVID-19, GI bleeding has been well described in the COVID-19 literature,1 , 2 critical and prolonged COVID-19 hospitalization courses may result in malnutrition, and acute pancreatitis has been described as an entity associated with COVID-19 infection.3 , 4 Pancreatitis was diagnosed based on the Atlanta classification. Clinical information was collected from electronic medical records using a standardized data collection sheet. We included malnutrition in the study because we have been anecdotally seeing patients with prior COVID-19 who are unable to have weight regain.
Patient charts were reviewed manually to confirm presence of GI manifestations at admission, GI bleeding and malnutrition during course of initial COVID-19 hospitalization, and evaluate symptoms at 3- and 6-months follow-up visits. Three-month follow-up criteria included outpatient visit or repeat hospitalization 3 months after initial hospitalization date (up to 6 months), and similarly 6-month follow-up was considered 6 months after initial hospitalization date. On manual chart review the following were excluded: those with anemia not secondary to GI bleeding, pancreatitis secondary to nonviral etiologies, and those patients with multiple gastroenteritis symptoms were consolidated (ie, if abdominal pain, nausea, and vomiting all present, patient was counted for this symptom 1 time in the gastroenteritis category). Our population cohort had a rate of irritable bowel syndrome and inflammatory bowel disease at 1 % and 2 %, respectively, and thus were not excluded from the study. Although there are a total number of patients in the study, some patients experienced 2 or more unique GI manifestations (ie, if GI bleeding and malnutrition both occurred in the same patient, this was counted as 2 distinct GI manifestations; however, 1 patient in the study overall).
Resolution of each symptom was determined via chart review: for gastroenteritis symptoms it is the resolution of abdominal pain, nausea, vomiting, diarrhea on subsequent follow-up; for GI bleeding it is the absence of repeat episode of GI bleeding on follow-up; for pancreatitis it is absence of recurrence of another acute pancreatitis episode/sequelae of pancreatitis; and for malnutrition based on the ability to have weight regain (the only objective marker that can be abstracted easily).
For those patients with symptoms of malnutrition, anorexia, and weight loss, weight assessments at admission, 3 months, and 6 months were documented. In addition those with malnutrition were documented as such on initial hospitalization via a nutrition consultation by a board-certified nutritionist. Descriptive statistical analysis was performed.
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