Although anecdotally coronavirus disease 2019 (COVID-19) presents most commonly with respiratory symptoms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) obtains cellular entry via the widely expressed angiotensin-converting enzyme 2 (ACE2) receptors, thus increasing the risk of not only respiratory but also alimentary tract involvement.1Guan W.J. et al.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (17406) Google Scholar, 2Hoffman M. et al.Cell. 2020; 181: 271-280Abstract Full Text Full Text PDF PubMed Scopus (11009) Google Scholar, 3Du M. et al.Gastroenterology. 2020; 158: 2298-2301.e7Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar Early reports from China have described gastrointestinal symptoms in as many as half of patients diagnosed with COVID-19; however, data regarding the potential gastrointestinal implications of COVID-19 among the US patient population remain limited.4Pan L. et al.Am J Gastroenterol. 2020; 115: 766-773Crossref PubMed Scopus (1009) Google Scholar, 5Zhou Z. et al.Gastroenterology. 2020; 158: 2294-2297Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar, 6Cheung K.S. et al.Gastroenterology. 2020; https://doi.org/10.1053/j.gastro.2020.03.065Abstract Full Text Full Text PDF Scopus (928) Google Scholar Therefore, we aimed to systematically characterize the prevalence and features of gastrointestinal manifestations associated with SARS-CoV-2 infection and evaluate gastrointestinal-specific health outcomes among a cohort of US adults. This was a multicenter cohort study performed across 9 hospitals (2 tertiary care and 7 community hospitals) in Massachusetts. All consecutive adults (age ≥18 years) hospitalized on or before April 2, 2020, were included. Only patients with laboratory-confirmed SARS-CoV-2 on polymerase chain reaction nasopharyngeal swab testing were included. Patient demographics; presenting systemic, respiratory, and gastrointestinal symptoms; comorbid conditions; laboratory data; and clinically relevant hospitalization outcomes (including intensive care unit (ICU) admission, need for mechanical ventilation, and in-hospital mortality) were obtained. The primary outcome was prevalence of any gastrointestinal symptoms in patients hospitalized with COVID-19 at initial presentation. Secondary analyses included associations between gastrointestinal symptoms and other clinical manifestations, laboratory results, patient characteristics, and hospital course. A total of 318 patients with confirmed COVID-19 were included. Patients were generally overweight to obese (mean body mass index, 30.0 ± 6.5 kg/m2), with a majority having cardiovascular risk factors or comorbid conditions. Baseline demographics were not different among those presenting with gastrointestinal symptoms compared to those without (Supplementary Table 1). Overall, 61.3% of patients reported at least 1 gastrointestinal symptom on presentation, most commonly loss of appetite (34.8%), diarrhea (33.7%), and nausea (26.4%) (Table 1). Gastrointestinal symptoms were the predominant presenting complaint among 20.3% of patients and the initial presenting symptoms of COVID-19 among 14.2% of individuals.Table 1Gastrointestinal Symptoms on Presentation of Hospitalized Patients With COVID-19 (N = 318)Gastrointestinal symptomsn (%)Any gastrointestinal symptoms195 (61.3)Loss of appetite110 (34.8)Diarrhea107 (33.7)Nausea84 (26.4)Vomiting49 (15.4)Abdominal pain46 (14.5)Weight loss30 (9.4)Constipation3 (0.94)Melena2 (0.63)Reflux2 (0.63)Dysphagia1 (0.31)Odynophagia1 (0.31)Hematochezia1 (0.31) Open table in a new tab Patients with gastrointestinal symptoms also reported significantly higher rates of fatigue (65.1% vs 45.5%; P = .0006), myalgia (49.2% vs 22%; P < .0001), and sore throat (21.5% vs 9.8%; P = .0064). Specifically, fatigue was more prevalent among patients with loss of appetite and diarrhea, whereas myalgia was more prevalent among those with loss of appetite, diarrhea, and nausea (all P < .05). Patients with diarrhea and nausea presented with higher rates of sore throat (Table 2).Table 2Respiratory and Constitutional Symptoms on Presentation of Hospitalized Patients with COVID-19SymptomsAll patients with COVID-19 (N = 318), n (%)GI symptoms (n = 195), n (%)No GI symptoms (n = 123), n (%)P valueGeneral symptoms Fever258 (81.3)161 (82.6)97 (78.9).41 Fatigue183 (57.5)127 (65.1)56 (45.5).0006 Myalgia123 (38.7)96 (49.2)27 (22.0)<.0001 Chills72 (22.6)50 (25.6)22 (17.9).11 Diaphoresis15 (4.7)12 (6.2)3 (2.4)0.13 Arthralgia8 (2.5)4 (2.1)4 (3.3).51Airway symptoms Cough247 (77.7)156 (80)91 (74.0).21 Dyspnea191 (60.1)107 (54.9)84 (68.3).02 Sore throat54 (17.0)42 (21.5)12 (9.8).0064 Sputum production45 (14.2)33 (16.9)12 (9.8).074 Rhinorrhea36 (11.4)26 (13.4)10 (8.1).15Loss of smell or taste41 (12.9)33 (16.9)8 (6.5).0064 Anosmia32 (10.1)26 (13.3)6 (4.9).0146 Ageusia24 (7.6)21 (10.9)3 (2.4).0057NOTE. Bold values highlight P-value <.05.GI, gastrointestinal. Open table in a new tab NOTE. Bold values highlight P-value <.05. GI, gastrointestinal. Additionally, loss of smell or taste was more common among patients with gastrointestinal symptoms (16.9% vs 6.5%; P = .0064). Anosmia and ageusia were associated with nausea (adjusted odds ratio, 2.71; 95% confidence interval, 1.21–6.20; P = .015) and loss of appetite (adjusted odds ratio, 3.70; 95% confidence interval, 1.49–9.16; P = .0048), even after controlling for potential confounders on multivariate analyses (Supplementary Table 2). No additional gastrointestinal symptoms were associated with either anosmia or ageusia or with other patient characteristics. Examination of laboratory test results obtained on admission showed no significant differences in leukocyte count, hemoglobin, platelets, coagulation factors, liver enzymes, and cardiac markers between patients with gastrointestinal symptoms and those without. Inflammatory markers including ferritin, D-dimer, and C-reactive protein were also similar between the 2 groups (Supplementary Table 1). A subgroup (n = 202) of included patients with COVID-19 had completed full hospitalizations at the time of data analysis. Among this group, 35 (17.5%) required a stay in the ICU, and 26 (13%) needed mechanical ventilation. There were 32 (15.8%) in-hospital deaths. No differences in rates of clinical deterioration were noted between patients with and without gastrointestinal symptoms when comparing ICU admission, need for mechanical ventilation, or overall mortality (Supplementary Table 1). In this multicenter study of 2 tertiary care and 7 community hospitals in the United States, we found that almost two thirds of patients hospitalized with SARS-CoV-2 infection presented with at least 1 gastrointestinal symptom. Loss of appetite and diarrhea were the most common, each present in approximately one third of patients, whereas nausea, vomiting, abdominal pain, and weight loss were each reported in 10%–25% of the cohort. Patients with gastrointestinal symptoms reported more fatigue, myalgia, and sore throat. There were no other significant differences in terms of patient demographics, medical history, presenting laboratory evaluations, clinical course, and hospitalization outcomes between patients with and without gastrointestinal symptoms. When gastrointestinal symptoms were individually evaluated, we observed significantly higher rates of nausea and loss of appetite among patients with anosmia and ageusia, both symptoms believed to be highly linked to COVID-19. The senses of taste and smell have previously been linked to upper gastrointestinal symptoms and disorders, changes in appetite, and food enjoyment.7Kabadi A. et al.J Neurogastroenterol Motil. 2017; 23: 370-377Crossref PubMed Scopus (12) Google Scholar,8Hutton J.L. et al.J Pain Symptom Manage. 2007; 33(2): 156-165Abstract Full Text Full Text PDF Scopus (164) Google Scholar This observation carries clinical significance in both the diagnosis and management of severe symptoms. Our data of patients with COVID-19 in the United States showed a similarly high prevalence of gastrointestinal symptoms compared to the published literature from China. However, other previously reported trends were not noted—specifically, no sex predilection, association with more severe disease, laboratory test result changes (higher leukocytes and transaminases), or significant differences in inflammatory markers were seen among patients with gastrointestinal symptoms.4Pan L. et al.Am J Gastroenterol. 2020; 115: 766-773Crossref PubMed Scopus (1009) Google Scholar,5Zhou Z. et al.Gastroenterology. 2020; 158: 2294-2297Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar These differences may be explained by variations in-patient clinical factors (medical history, body habitus, home medication), environmental and social/cultural factors (living conditions, daily habits, diet, mode of transmission), and hospitalization practices between China and the United States with regard to COVID-19. Specific limitations to this study include the retrospective design, lack of validated symptom instruments, and focus on in-hospital outcomes, because we excluded ambulatory patients with perhaps less severe disease or milder symptoms. Despite these limitations, this is one of the first and largest US studies to date to systematically evaluate gastrointestinal manifestations of COVID-19. Our study included patients hospitalized in both tertiary care and community settings, which makes the demonstrated results more generalizable to the US patient population at large. In conclusion, in our cohort of hospitalized US adults, approximately two thirds of patients with COVID-19 reported at least 1 gastrointestinal symptom, with loss of appetite and diarrhea being the most common. Although we did not find a correlation between the presence of gastrointestinal symptoms and hospitalization outcomes, we noted that the cardinal COVID-19 symptoms of anosmia and ageusia were independently predictive of nausea and anorexia at presentation. Further studies are needed to investigate the value and clinical utility of gastrointestinal-specific testing for SARS-CoV-2 to help improve diagnosis and reduce transmission. Walker D. Redd, MD (Conceptualization: Lead; Data curation: Equal; Formal analysis: Equal; Investigation: Lead; Methodology: Lead; Writing – original draft: Lead; Writing review & editing: Lead). Joyce C. Zhou, BA (Data curation: Equal; Investigation: Equal; Writing – original draft: Lead; Writing – review & editing: Equal). Kelly E. Hathorn, MD (Data curation: Equal; Investigation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Thomas R. McCarty, MD (Data curation: Equal; Formal analysis: Equal; Investigation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Ahmad Najdat Bazarbashi, MD (Data curation: Equal; Formal analysis: Equal; Investigation: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Christopher C. Thompson, MD, MSc (Formal analysis: Equal; Resources: Equal; Visualization: Equal; Writing – original draft: Equal; Writing – review & editing: Equal). Lin Shen, MD (Conceptualization: Equal; Data curation: Lead; Investigation: Equal; Methodology: Lead; Writing – review & editing: Equal). Walter W. Chan, MD, MPH (Conceptualization: Lead; Data curation: Lead; Formal analysis: Lead; Investigation: Lead; Methodology: Lead; Project administration: Lead; Resources: Lead; Software: Lead; Supervision: Lead; Writing – original draft: Lead). Continuous variables were expressed as means with standard deviations, and categorical data were reported using numbers and frequencies. On univariate analyses, Student t test and Fisher exact test were used for continuous variables and categorical variables, respectively. Multivariate analyses were performed by using logistic regression, with covariates chosen a priori based on clinical judgment. Two-tailed P values of .05 or lower were considered statistically significant. This study was approved by the Partners Healthcare institutional review board (2020P0000983).Supplementary Table 1Baseline Clinical Characteristics, Laboratory Values on Admission, and Hospitalization Outcomes of COVID-19 Patient CohortPatient CharacteristicsAll patients with COVID-19 (N = 318)GI symptoms (n = 195)No GI symptoms (n = 123)P valueAge, y, mean ± SD63.4 ± 16.662.3 ± 15.965.0 ± 17.6.16Female, n (%)144 (45.3)93 (47.7)51 (35.4).28BMI, kg/m2, mean ± SD30.0 ± 6.530.5 ± 6.729.3 ± 6.2.11Past medical history, n (%) Coronary artery disease46 (14.5)26 (13.3)20 (16.3).47 Congestive heart failure31 (9.8)16 (8.3)15 (12.2).25 Cardiac arrhythmia48 (15.1)26 (13.3)22 (17.9).27 Hypertension188 (59.1)111 (56.9)77 (62.6).32 Hyperlipidemia146 (45.9)89 (45.6)57 (46.3).90 Diabetes105 (33.1)62 (32.0)43 (35.0).58 Cerebrovascular accident11 (3.5)8 (4.1)3 (2.4).42 Pulmonary disorders67 (21.1)40 (20.5)27 (22.0).76 Chronic renal insufficiency40 (13.8)20 (11.7)20 (17.0).20 Thyroid disorders45 (14.2)29 (14.9)16 (13.0).64 Gastroesophageal reflux disease80 (25.2)48 (24.6)32 (26.0).78 Irritable bowel syndrome5 (1.6)2 (1.04)3 (2.4).24 Inflammatory bowel disease4 (1.3)3 (1.5)1 (0.81).72 Peptic ulcer disease9 (2.8)7 (3.6)2 (1.6).31 Helicobacter pylori infection10 (3.1)8 (4.1)2 (1.6).22 Other GI disorders14 (4.4)9 (4.7)5 (4.1).44Social history, n (%) Alcohol use39 (12.3)28 (14.4)11 (8.9).15 Tobacco use35 (11.0)23 (11.8)12 (9.8).57Laboratory test results, mean ± SD White blood cell count, ×109/L7.8 ± 10.27.3 ± 8.78.5 ± 12.2.16 Lymphocytes, ×109/L9.1 ± 17.27.8 ± 11.611.2 ± 23.5.14 Hemoglobin, g/L19.3 ± 13.919.6 ± 12.119.0 ± 16.3.73 Platelets, ×109/L196.5 ± 82.7198.6 ± 80.1193.2 ± 86.8.27 INR1.2 ± 0.501.2 ± 0.481.3 ± 0.5.47 PTT, seconds36.8 ± 15.735.8 ± 11.637.8 ± 18.8.52 AST, U/L50.2 ± 59.246.7 ± 35.355.7 ± 84.2.26 ALT, U/L36.0 ± 31.335.9 ± 31.836.1 ± 30.7.97 Alkaline phosphate, mmol/L80.5 ± 38.380.1 ± 38.181.2 ± 38.8.81 Total bilirubin, mmol/L0.63 ± 1.090.54 ± 0.300.78 ± 1.72.13 NT-pro BNP, pg/mL1302 ± 31731136 ± 28331536 ± 3606.44 D-dimer, nmol1726 ± 54251419 ± 83102220 ± 8310.33 Ferritin, ug/L837 ± 1117827 ± 837853 ± 1448.87 Lactate, mmol/L1.58 ± 0.941.46 ± 0.641.77 ± 1.25.04 C-reactive protein, mg/L91.7 ± 79.288.8 ± 74.2103.2 ± 85.5.24Hospitalization outcomesaSubgroup including only patients who have completed a full hospitalization (discharged or death). (n = 202), n (%) ICU stay35 (17.5)20 (15.4)15 (21.4).28 Mechanical ventilation26 (13.0)14 (10.9)12 (16.0).22 Death32 (15.8)16 (12.2)16 (22.5).06NOTE. Bold values denote P<.05.ALT, alanine aminotransferase; AST, aspartate aminotransferase; GI, gastrointestinal; INR, international normalized ratio; NT-pro BNP, N-terminal pro-B–type natriuretic peptide; PTT, partial thromboplastin time; SD, standard deviation.a Subgroup including only patients who have completed a full hospitalization (discharged or death). Open table in a new tab Supplementary Table 2Multivariate Models for Predictors of Nausea and Loss of Appetite on Presentation Among Hospitalized Patients With COVID-19CovariatesOdds ratio95% confidence intervalP valueMultivariate regression model for nauseaAnosmia2.921.28–6.68.01Age0.980.97–1.01.19Sex0.470.28–0.81.01BMI0.970.93–1.01.10History of upper GI conditionsaHistory of upper GI conditions includes a history of gastroesophageal reflux disease, gastroparesis, peptic ulcer disease, and Helicobacter pylori infection.0.850.46–1.57.60Tobacco use1.520.68–3.40.31Alcohol intake0.440.17–1.16.09Multivariate regression model for anorexiaCovariatesOdds ratio95% confidence IntervalP valueAgeusia3.531.41–8.84.007Age0.990.97–1.00.10Sex0.750.46–1.24.26BMI1.00.96–1.04.92History of upper GI conditionsaHistory of upper GI conditions includes a history of gastroesophageal reflux disease, gastroparesis, peptic ulcer disease, and Helicobacter pylori infection.1.40.80–2.44.23Tobacco use1.680.80–3.54.17Alcohol intake2.251.09–4.65.03NOTE. Bold values denote P<.05.BMI, body mass index; GI, gastrointestinal.a History of upper GI conditions includes a history of gastroesophageal reflux disease, gastroparesis, peptic ulcer disease, and Helicobacter pylori infection. Open table in a new tab NOTE. Bold values denote P<.05. ALT, alanine aminotransferase; AST, aspartate aminotransferase; GI, gastrointestinal; INR, international normalized ratio; NT-pro BNP, N-terminal pro-B–type natriuretic peptide; PTT, partial thromboplastin time; SD, standard deviation. NOTE. Bold values denote P<.05. BMI, body mass index; GI, gastrointestinal.