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Background COVID-19 was initially described as a severe acute respiratory disease that could drive to pneumonia, compromising the life of the patients in the worst scenario. However, even though in most of the cases the respiratory symptoms are still the most common manifestations of the disease, nowadays it is considered as a complex multisystem illness, affecting a variety of organs and tissues. Asymptomatic and atypic cases have also been described, where symptoms are not related to those first described, as is the case of this report. Case presentation On November 23, 2020, a 53-year-old woman goes to the emergency room due to gastrointestinal symptoms. The admission diagnosis was inflammatory bowel disease and a mild event of idiopathic chronic ulcerative colitis, and the initial treatment was focused on the metabolic acidosis, and the reestablishment the hydroelectrolytic and hemodynamic balance. Then, she was transferred to the Gastroenterology Unit where she was treated for one week. During her hospitalization, she showed a refractory shock caused by progressive organ deterioration (renal and neurological), requiring a double-vasopressor support, oxygenation, and ventilation. Considering the laboratory tests results and computed tomography scans, a COVID-19 test was carried out, obtaining a positive result with a high viral load. The S gene of the virus was amplified and sequenced, finding an uncommon mutation rarely reported worldwide. After considerable systemic deterioration, the patient presented cardiorespiratory arrest, with no response and died on December 1, after 8 days of hospitalization. Conclusions In this report we describe the pathogenesis, clinical manifestations, and outcome of a patient with atypical COVID-19 symptoms (mainly gastrointestinal), rapidly evolving and with lethal consequences. Therefore, it is important to emphasize the need to strengthen patient surveillance in health centers, including those who do not present typical symptoms of COVID-19. In addition, it will be important to track the identified mutation (H1058Y) in the S viral gene and assess whether it could be associated with a different clinical manifestation of the disease or if it was just an isolated event.