Abstract
This cohort study compares the incidence of gastrointestinal complications (transaminitis, ileus, Ogilvie syndrome, mesenteric ischemia) among critically ill patients with coronavirus disease 2019 (COVID-19)– vs non–COVID-19–induced acute respiratory distress syndrome (ARDS) at a single US academic hospital between March and May 2020.
Coronavirus disease 2019 (COVID-19) appears to have significant extrapulmonary complications affecting multiple organ systems.1,2,3 Critically ill patients with COVID-19 often develop gastrointestinal complications during their hospital stay, including bowel ischemia, transaminitis, gastrointestinal bleeding, pancreatitis, Ogilvie syndrome, and severe ileus.3 Whether the high incidence of gastrointestinal complications is a manifestation of critical illness in general or is specific to COVID-19 remains unclear. We compared the incidence of gastrointestinal complications of critically ill patients with COVID-19–induced acute respiratory distress syndrome (ARDS) vs comparably ill patients with non–COVID-19 ARDS using propensity score analysis.
Methods
All patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on reverse transcriptase–polymerase chain reaction who were intubated and admitted to 1 of 13 (preexistent and surge) intensive care units (ICUs) of Massachusetts General Hospital between March 13, 2020, and May 7, 2020, were included, then matched to a cohort of patients admitted between 2018 and 2019 and meeting the Berlin criteria for ARDS.4 No changes occurred in the ICU staffing models or protocols of care of ARDS during the study period. Propensity score matching was performed adjusting for demographics (eg, age, sex, body mass index, smoking status), comorbidities (eg, chronic lung/kidney disease, congestive heart failure, coronary artery disease, hypertension, diabetes), and severity of illness on ICU admission (Sequential Organ Failure Assessment score). We examined in both groups the following gastrointestinal complications: transaminitis, ileus, Ogilvie syndrome, and mesenteric ischemia.
Wilcoxon rank sum, Pearson χ2, and Fisher exact tests were used, as appropriate. To determine whether differences in the duration of illness between groups might contribute, incidence rate ratios and Kaplan-Meier curves looking at time to development of the complication from hospital admission were calculated. All tests were 2-tailed; statistical significance was defined as P < .05. Statistical analyses were performed on Stata version 15.0 (StataCorp LP). The Mass General Brigham Institutional Review Board ruled this study exempt including a waiver of informed consent.
Results
A total of 486 patients with ARDS met eligibility criteria, of which 244 had non–COVID-19 ARDS and 242 had COVID-19 ARDS. This report includes data from 141 patients with COVID-19 (58%) whose overall gastrointestinal complications have been previously described.3 The median age of patients was 60.5 years (interquartile range, 48-71 years) and 62 years (interquartile range, 53-73.5) years for patients with and without COVID-19, respectively, and the percentage of males was 66.5% and 54.9%, respectively.
Ninety-two patients with COVID-19 and ARDS were propensity score matched to 92 patients with non–COVID-19 ARDS (Table). The etiologies for ARDS among the non–COVID-19–matched cohort were bacterial pneumonia (60%), aspiration (27%), influenza (7%), respiratory syncytial virus infection (2%), and Pneumocystis jiroveci pneumonia (2%). Patients with COVID-19 were more likely to develop gastrointestinal complications compared with those without COVID-19 (74% vs 37%; P < .001; incidence rate ratio, 2.33 [95% CI, 1.52-3.63]). The difference in incidence was more evident after the third day of critical illness (Figure). Specifically, patients with COVID-19 developed more transaminitis (55% vs 27%; P < .001), severe ileus (48% vs 22%; P < .001), and bowel ischemia (4% vs 0%; P = .04). Three of the 4 patients with COVID-19 and bowel ischemia were taken to the operating room and had intraoperative findings consistent with COVID-19 bowel as previously described in different patients.3 Pathology findings demonstrated fibrin thrombi in the microvasculature underlying areas of necrosis.
Table. Baseline Population Characteristics and Outcomes.
| Characteristic/outcome | No. (%) | P value | |
|---|---|---|---|
| Non–COVID-19 ARDS | COVID-19 ARDS | ||
| Prematching characteristics | |||
| No. of patients | 244 | 242 | |
| Age, median (IQR), y | 62 (53-73.5) | 60.5 (48-71) | .09 |
| BMI, median (IQR)a | 27.5 (23-32) | 30 (27-35) | <.001 |
| Sex | |||
| Female | 110 (45.1) | 81 (33.5) | .009 |
| Male | 134 (54.9) | 161 (66.5) | |
| Smoking | 164 (67.2) | 68 (28.1) | <.001 |
| SOFA score, median (IQR) | 7 (5-9) | 6 (4-8) | <.001 |
| Comorbidities | |||
| Hypertension | 144 (59.0) | 128 (52.9) | .17 |
| Chronic lung diseaseb | 104 (42.6) | 51 (21.1) | <.001 |
| Diabetes | 64 (26.2) | 109 (45.0) | <.001 |
| Congestive heart failure | 56 (23.0) | 19 (7.9) | <.001 |
| Coronary artery disease | 45 (18.4) | 25 (10.3) | .01 |
| Chronic kidney disease | 42 (17.2) | 38 (15.7) | .65 |
| Postmatching characteristics | |||
| No. of patients | 92 | 92 | |
| Age, median (IQR), y | 64.5 (51.5-75.5) | 62 (48.5-71.5) | .24 |
| BMI, median (IQR)a | 28 (25-33.5) | 29 (25-32.5) | .55 |
| Sex | |||
| Female | 40 (43) | 38 (41) | .77 |
| Male | 52 (57) | 54 (59) | |
| Smoking | 39 (42) | 36 (39) | .65 |
| SOFA score, median (IQR) | 7 (4-8.5) | 7 (5-9) | .86 |
| Comorbidities | |||
| Hypertension | 50 (54) | 51 (55) | .88 |
| Diabetes | 35 (38) | 34 (37) | .88 |
| Chronic lung disease | 29 (32) | 27 (29) | .75 |
| Chronic kidney disease | 17 (18) | 18 (20) | .85 |
| Coronary artery disease | 14 (15) | 12 (13) | .67 |
| Congestive heart failure | 13 (14) | 15 (16) | .68 |
| Outcomes | |||
| No. of patients | 92 | 92 | |
| Pao2:Fio2 ratioc | 168 (136-228) | 191.5 (145.5-331) | .05 |
| Any gastrointestinal complication | 34 (37) | 68 (74) | <.001 |
| Transaminitis | 25 (27) | 51 (55) | <.001 |
| Ileus | 20 (22) | 44 (48) | <.001 |
| Ogilvie syndrome | 1 (1) | 2 (2) | .56 |
| Mesenteric ischemia | 0 | 4 (4) | .04 |
| 30-d Mortality | 21 (23) | 23 (25) | .73 |
| Hospital LOS, median (IQR) | 14 (9-24) | 24 (13-36) | <.001 |
| ICU LOS, median (IQR) | 8.5 (4.5-15) | 17 (8-25) | <.001 |
| Days on opioid drip, median (IQR) | 9 (4-15) | 1 (0-4.5) | <.001 |
| Days on ventilation, median (IQR) | 6 (3-11) | 13.5 (8.5-22.5) | <.001 |
| Tracheostomy | 11 (12) | 28 (30) | .002 |
| Emergency department readmission | 10 (11) | 10 (11) | .98 |
| Other complications | |||
| Venous thromboembolism | 6 (7) | 9 (10) | .42 |
| Acute kidney injury | 63 (68) | 72 (78) | .13 |
| Dialysisd | 14 (22) | 21 (29) | .36 |
Abbreviations: ARDS, acute respiratory distress syndrome; BMI, body mass index; COVID-19, coronavirus disease 2019; Fio2, fraction of inspired oxygen; ICU, intensive care unit; IQR, interquartile range; LOS, length of stay; Pao2, partial pressure of arterial oxygen; SOFA, Sequential Organ Failure Assessment.
Calculated as weight in kilograms divided by height in meters squared.
Includes asthma, chronic obstructive pulmonary disease, and interstitial lung disease.
Pao2:Fio2 ratio on admission to the ICU.
Percentage is of patients with acute kidney injury.
Figure. Kaplan-Meier Curves of Gastrointestinal Complications in Patients With Acute Respiratory Distress Syndrome (ARDS) With and Without Coronavirus Disease 19 (COVID-19).
The 2 curves initially look similar but start separating around day 3 of the intensive care unit stay.
Discussion
This study found a higher rate of gastrointestinal complications, including mesenteric ischemia, in critically ill patients with COVID-19 compared with propensity score–matched patients without COVID-19, suggesting a distinct phenotype for COVID-19 compared with conventional ARDS. High expression of angiotensin-converting enzyme 2 receptors along the epithelial lining of the gut that act as host-cell receptors for SARS-CoV-2 could explain involvement of abdominal organs.5 Higher opioid requirements and COVID-19–induced coagulopathy may also explain the disproportionately high rate of ileus and ischemic bowel disease.2 Differences in duration of illness did not seem to explain the differences in gastrointestinal complications. Limitations of this study include the single center and the unavailability of inflammatory markers to use for matching. Further translational studies are warranted to examine the pathophysiology of these findings.
Section Editor: Jody W. Zylke, MD, Deputy Editor.
References
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