COVID-19 Infection Manifesting as a Severe Gastroparesis Flare: A Case Report


 Background: Coronavirus Disease 2019 (COVID-19) is a disease caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which commonly presents with symptoms including fever, cough, and dyspnea. More recently, however, some patients have tested positive for COVID-19 after developing gastrointestinal (GI) symptoms either solely or in conjunction with respiratory symptoms. This may be due to SARS-CoV-2 infection of the GI tract. In patients with chronic GI illnesses, COVID-19 may initially present as a flare of their underlying GI conditions as viruses have historically been implicated in exacerbations of GI disorders, including gastroparesis. Case presentation: We report a case of a 37 year-old female with a history of diabetic gastroparesis who presented to the Emergency Department (ED) in a gastroparesis flare. Her symptoms in the ED failed to improve with fluids and anti-emetic medications. After developing a fever, she was tested and found to be positive for COVID-19.Conclusion: To our knowledge, at the present time, this is the first report of a patient with COVID-19 presenting with signs and symptoms of a gastroparesis flare. This case illustrates that patients with underlying GI disorders, such as gastroparesis, may have SARS-CoV-2 infections that present as an exacerbation of their underlying disorder. Initial presentation of these patients manifesting as a flare of their chronic GI disease, more severe than usual, should prompt an index of suspicion for COVID-19.

now treated with insulin. Prior upper endoscopy was negative and prior gastric emptying study was signi cant for 87% retention of radiolabeled meal at two hours (normal<60%) and 77% at four hours (normal<10%). At presentation in the ED, the emesis was non-bloody, non-bilious, and associated with mild epigastric pain. Review of systems was negative for fevers or respiratory symptoms. Vital signs were within normal range. The cause of her symptoms was initially attributed to a gastroparesis are in the setting of medication non-compliance as she had multiple ED visits in the past with similar presentations controlled with pharmacological treatment. She was discharged after a trial of metoclopramide administration. She returned the next day with worsening nausea and vomiting, which were described as signi cantly increased from her baseline gastroparesis ares, refractory to pharmacological therapy. Vitals were signi cant for a temperature of 100.4°F. Laboratory tests were notable for a Hemoglobin A1c of 7.2% (normal: 4.7 -6.4%) and a lymphopenia (white blood cell count: 3.4 K/mm 3 , normal: 4.0 -11.0 K/mm 3 ), reduced by about 5 K/mm 3 from her baseline. Six hours after initial triage, she developed a fever of 101.4°F. A chest x-ray and the CT Abdomen and Pelvis were unremarkable. The CT Chest ( g. 1), however, showed multi-focal ground glass opacities predominantly in the lung bases compatible with a viral/atypical pneumonia. A nasopharyngeal COVID-19 test was obtained, antibiotics were started empirically, and she was admitted to the hospital. On day 2 of admission, the gastroenterology service was consulted for the management of her gastroparesis are and recommended continuing pantoprazole, changing the administration of ondansetron and metoclopramide to standing medications, and starting mirtazapine. During this time, her COVID-19 test resulted positive. She was started on antibiotics (azithromycin and ceftriaxone), steroids, and entered into a Remdesivir clinical trial. Her aspartate aminotransferase values had an upward trend from Day 2 to Day 3: 21 U/L, 21 U/L, 40 U/L, 50U/L, normal range: 15 -37 U/L). Her GI symptoms improved and she became afebrile by day 4, and she was discharged on day 5. She was instructed to continue taking mirtazapine and ondansetron to manage her gastroparesis as well as antibiotics, steroids, and Remdesivir for COVID-19.

Discussion And Conclusion
This case report illustrates that COVID-19 infection can present as a are of gastroparesis. The important take home message is that in patients with an exacerbation of a chronic illness, such as gastroparesis, one should consider COVID-19 as a potential etiology for the worsening of a previously stable chronic disorder.
The majority of patients with COVID-19 have currently presented with respiratory symptoms 1,6 . However, more patients are starting to present with GI symptoms either solely or in conjunction with pulmonary manifestations 3,7 . This involvement with the GI tract has also been re ected in reports of patients testing positive for infection in fecal samples, some of these negative in nasopharyngeal and sputum samples 8 . Immuno uorescence studies by Xiao et. al have shown that the SARS-CoV-2 ACE2 protein cell receptor is expressed in the glandular cells of gastric, duodenal, and rectal epithelia potentially allowing viral entry into these cells 9 . These are the same cell receptors found in the bronchial epithelial cells in the lower respiratory tract responsible for SARS-CoV-2 infection in the respiratory system 10 . Other coronaviruses that have also caused respiratory syndromes such as Middle East Respiratory Syndrome Coronavirus and SARS-CoV-1 have similarly been found to infect intestinal cells and spread through a fecal-oral route [11][12][13] . Taken together, it may be possible that the GI tract is also serving as a nidus for SARS-CoV-2 infection. Though, the predilection of SARS-CoV-2 for either the pulmonary system or the GI tract is not well understood despite similar infection mechanisms.
In epidemiologic studies, comorbidities of patients may be a risk factor for infection with SARS-CoV-2. In a meta-analysis including 1,576 patients, respiratory system diseases were among the most prevalent comorbidities affecting those with COVID-19 presenting primarily with respiratory symptoms 14 . Furthermore, Leung et. al found that patients with Chronic Obstructive Pulmonary Disease (COPD) have upregulated airway expression of the ACE2 protein cell receptor, which may increase the risk of patients with COPD to SARS-CoV-2 infection 10 . This suggests that comorbidities may play a role in the pathogenesis of SARS-CoV-2. In a recent study of 116 patients with COVID-19 who initially presented with cough, fever, and dyspnea as the main presenting symptoms, nearly a third of the patients were reported to develop GI symptoms later in the course of their infection 5 . In this series, 20.7% of patients had chronic pulmonary disorders and 26.1% had a smoking history, while there were no patients with underlying GI disorders and only 2.8% had chronic liver disease. The pulmonary comorbidities may have served as a risk factor for initial pulmonary infection in this cohort of patients. The infection may have subsequently propagated to the GI tract, demonstrated by the delay in GI symptoms, as receptors for SARS-CoV-2 have been found to be present in multiple organ systems 15 . This would suggest that comorbidities may play a key role in the initial pathogenesis of SARS-CoV-2. In the context of our patient, this may explain why she developed evidence of pulmonary disease on imaging despite presenting solely with GI symptoms. Her underlying gastroparesis may have predisposed her to infection with SARS-CoV-2 in the GI tract as evidenced by her symptom severity and uptrending liver enzyme values 16 . Her infection may have subsequently spread to her lungs as manifested by the multi-focal ground glass opacities found on imaging. Further research is needed to determine if patients are at higher risk for SARS-CoV-2 infection in the GI tract with certain chronic GI conditions.
Though it is possible that her intractable nausea and vomiting were entirely independent of her gastroparesis perhaps due to the COVID-19 virus infection itself, an exacerbation of gastroparesis from the COVID-19 virus is the likely scenario, as viruses have been implicated in the pathogenesis of gastroparesis 17,18 . In one study investigating the etiology of the disorder, 23% of patients with gastroparesis have been described as having postinfectious gastroparesis from a prior viral infection 19 .
The proposed mechanism by which viruses can induce gastroparesis is through an acute injury to either the neural innervation of the stomach or the interstitial cells of Cajal in the stomach causing delayed gastric emptying 20 . Similarly, infections have also been implicated in worsening of other chronic GI disorders, such as in ammatory bowel disease (IBD) 21 . Kim et. al found that patients with ulcerative colitis (UC) with concomitant cytomegalovirus (CMV) infections had a higher frequency of IBD-related hospitalizations compared to patients with UC without CMV infections 22 . This increased morbidity in the cohort with CMV infections may be due to the ability of CMV proteins to enhance pro-in ammatory cytokines to worsen the in ammation causing a are of their UC more severe than baseline 23 . Therefore, it is reasonable to suspect that a virus like SARS-CoV-2 could potentially exacerbate an underlying GI disorder causing a are of the disease during the initial presentation of COVID-19.
To our knowledge, at the present time, this is the rst case of COVID-19 initially manifesting with signs and symptoms of a gastroparesis are. This unique case illustrates that patients with underlying GI disorders, such as gastroparesis, may be at risk for SARS-CoV-2 infection of the GI tract. Initial presentation of these patients may manifest as a are of their chronic GI disease, more severe than usual -either from worsening of their underlying disorder, or symptoms from the COVID-19 virus itself.