This case report illustrates that COVID-19 infection can present as a flare 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 symptoms1,6. However, more patients are starting to present with GI symptoms either solely or in conjunction with pulmonary manifestations3,7. This involvement with the GI tract has also been reflected in reports of patients testing positive for infection in fecal samples, some of these negative in nasopharyngeal and sputum samples8. Immunofluorescence 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 cells9. 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 system10. 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 route11–13. 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 symptoms14. 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 infection10. 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 infection5. 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 systems15. 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 values16. 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 gastroparesis17,18. 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 infection19. 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 emptying20. Similarly, infections have also been implicated in worsening of other chronic GI disorders, such as inflammatory 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 infections22. This increased morbidity in the cohort with CMV infections may be due to the ability of CMV proteins to enhance pro-inflammatory cytokines to worsen the inflammation causing a flare of their UC more severe than baseline23. Therefore, it is reasonable to suspect that a virus like SARS-CoV-2 could potentially exacerbate an underlying GI disorder causing a flare of the disease during the initial presentation of COVID-19.
To our knowledge, at the present time, this is the first case of COVID-19 initially manifesting with signs and symptoms of a gastroparesis flare. 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 flare of their chronic GI disease, more severe than usual – either from worsening of their underlying disorder, or symptoms from the COVID-19 virus itself.