Don't Overlook Digestive Symptoms in Patients With 2019 Novel Coronavirus Disease (COVID-19)
Authors: Shihua Luo, Xiaochun Zhang, Haibo Xu
Journal: Clinical Gastroenterology and Hepatology (2020)

In late December 2019, a cluster of patients with pneumonia of unknown cause was linked epidemiologically to a seafood and wet animal wholesale market in Wuhan City, China. The causative pathogen subsequently was identified as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1Emerging understandings of 2019-nCoV.Lancet. 2020; 135: 311Google Scholar Over the course of the current pandemic, it became apparent that some patients can present with abdominal symptoms without fever or respiratory manifestations, and could be overlooked by health care providers. We present a case series of hospitalized patients with SARS-CoV-2 infection whose initial symptoms were gastrointestinal. This retrospective study was approved by the Medical Ethical Committee of Zhongnan Hospital of Wuhan University. We evaluated all 1141 cases of 2019 novel coronavirus disease (COVID-19) admitted to Zhongnan Hospital of Wuhan University from January 1, 2020, to February 20, 2020. A diagnosis of COVID-19 pneumonia was based on the COVID-19 Prevention and Control Program (4th edition) published by the National Health Commission of China.2National Health Commission of ChinaNew coronavirus pneumonia prevention and control program (in Chinese). 4th ed. January 22, 2020.http://www.gov.cn/zhengce/zhengceku/2020-01/28/5472673/files/0f96c10cc09d4d 36a6f9a9f0b42d972b.pdfDate accessed: February 4, 2020Google Scholar All patients received chest computed tomography (CT) and had throat-swab specimens obtained and maintained in viral-transport media. Reverse-transcription polymerase chain reaction detection reagents were provided by the Center for Disease Control and Prevention, Wuhan, Hubei Province. Laboratory confirmation of COVID-19 was performed both in our hospital and the Center for Disease Control and Prevention laboratory of Hubei Province. Confirmed cases of COVID-19 infection were defined as those with a positive test result from either laboratory.3WHOLaboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases.Interim guidance. January 17, 2020; (Available from:)https://www.who.int/publications-detail/laboratory-testing-for-2019-novel-coronavirus-in-suspected-human-cases-20200117Date accessed: February 4, 2020Google Scholar Of 1141 confirmed COVID-19 cases, 183 (16%) presented with gastrointestinal symptoms only, and their clinical characteristics are summarized in Table 1. Men slightly outnumbered women, and the most common gastrointestinal symptom was loss of appetite, followed by nausea and vomiting, which occurred in approximately two thirds of cases. Diarrhea and abdominal pain were the presenting symptom in 37% and 25% of patients, respectively.Table 1Patients With COVID-19 Infection Presenting With Gastrointestinal SymptomsClinical characteristics/cases (N = 183)N (%)P valueSex.032 Male102 (56) Female81 (44)Age, y53.8Epidemiologic history.063 Environmental exposure94 (51) Close contact99 (54)Gastrointestinal symptoms Nausea134 (73) Vomiting119 (65) Abdominal pain45 (25) Diarrhea68 (37) Loss of appetite180 (98) Both nausea and vomiting37 (20) Both abdominal pain and diarrhea16 (9) All symptoms12 (7)Laboratory characteristics Leukocytes, 3.5–9.5 ×109/L2.7 ± 0.2 Lymphocytes, 1.1–3.2 ×109/L0.53 ± 0.014 C-reactive protein, 0.0–10.0 mg/L18.7 ± 6.8 Aspartate aminotransferase, 15–40 U/L65.8 ± 12.7 Alanine aminotransferase, 9–50 U/L66.4 ± 13.2 Blood urea nitrogen, 2.8–7.6 mmol/L6.4 ± 2.5 Creatinine, 64–104 μmol/L85.7 ± 37.2Chest CT findings175 Unilateral107 (61) Bilateral68 (39) Abnormal lung texture145 (83) Ground-glass shadow128 (73) Pulmonary consolidation47 (27) Unilateral pleural effusion13 (7) Bilateral pleural effusion7 (4)COVID-19, 2019 novel coronavirus disease; CT, computed tomography. Open table in a new tab COVID-19, 2019 novel coronavirus disease; CT, computed tomography. Laboratory testing showed that mean leukocyte (2.7 ± 0.2 ×109/L) and lymphocyte (0.53 ± 0.014 ×109/L) counts were below normal, and C-reactive protein levels were increased (18.7 ± 6.8 mg/L). Mild increases in serum aminotransferases were noted (aspartate aminotransferase, 65.8 ± 12.7 U/L; alanine aminotransferase, 66.4 ± 13.2 U/L), but renal function generally was intact. At the onset of their illness, 175 of 183 (96%) of patients had lung lesions on chest CT, which were unilateral in 61% of cases. The most common CT findings were abnormal lung texture (83%), ground-glass densities (73%), consolidation (27%), and pleural effusion (11%). The mean time elapsed for confirmation of COVID-19 was 3.5 days from the onset of symptoms. Of the 183 patients, 7 died of progressive respiratory failure, and 176 recovered. Patients with COVID-19 typically present with fever or a respiratory syndrome. Our case series shows that some patients can present with gastrointestinal symptoms, with a paucity of other manifestations. Such patients could be overlooked, leading to potentially serious consequences to them and their contacts. It is important that clinicians are aware that COVID-19 can present with predominantly gastrointestinal symptoms, and maintain appropriate vigilance and a high index of suspicion. SARS-CoV-2 can enter angiotensin converting enzyme II (ACE2)-expressing cells. ACE2 is expressed not only in lung alveolar type 2 cell, but also can be found in the upper esophagus, and in stratified epithelial cells and absorptive enterocytes in the ileum and colon.4Gui M. Song W. Zhou H. et al.Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding.Cell Res. 2017; 27: 119-129Crossref PubMed Scopus (432) Google Scholar The enteric symptoms of SARS-CoV-2 may be associated with invaded ACE2-expressing enterocytes.5Zhou P.Y.X. Wang X.I.G. Hu B. et al.Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin.bioRxiv. 2020; https://doi.org/10.1101/2020.01.22.914952Crossref Google Scholar These findings suggest that the digestive system, along with the respiratory tract, may be a potential route for SARS-CoV-2 infection, and could explain why some patients present with gastrointestinal symptoms. Much still needs to be learned about this zoonotic coronavirus that has crossed species to infect human populations,6Zhu N. Zhang D.Y. Wang W.L. et al.A novel coronavirus from patients with pneumonia in China, 2019.N Engl J Med. 2020; 382: 727-733Crossref PubMed Scopus (18375) Google Scholar and its spectrum of disease.