Exclusion of nausea (N) and vomiting (V) from detailed consideration as symptoms of COVID-19 is surprising as N can be an early presenting symptom. We examined the incidence of NV during infection before defining potential mechanisms. We estimate that the overall incidence of nausea (median 10.5%), although variable, is comparable with diarrhea. Poor definition of N, confusion with appetite loss, and reporting of N and/or V as a single entity may contribute to reporting variability and likely underestimation. We propose that emetic mechanisms are activated by mediators released from the intestinal epithelium by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) modulate vagal afferents projecting to the brainstem and after entry into the blood, activate the area postrema (AP) also implicated in anorexia. The receptor for spike protein of SARS-CoV-2, angiotensin 2 converting enzyme (ACE2), and transmembrane protease serine (for viral entry) is expressed in upper gastrointestinal (GI) enterocytes, ACE2 is expressed on enteroendocrine cells (EECs), and SARS-CoV-2 infects enterocytes but not EECs (studies needed with native EECs). The resultant virus-induced release of epithelial mediators due to exocytosis, inflammation, and apoptosis provides the peripheral and central emetic drives. Additionally, data from SARS-CoV-2 show an increase in plasma angiotensin II (consequent on SARS-CoV-2/ACE2 interaction), a centrally (AP) acting emetic, providing a further potential mechanism in COVID-19. Viral invasion of the dorsal brainstem is also a possibility but more likely in delayed onset symptoms. Overall, greater attention must be given to nausea as an early symptom of COVID-19 and for the insights provided into the GI effects of SARS-CoV-2.
Keywords: ACE2; COVID-19; SARS-CoV-2; angiotensin II; angiotensin converting enzyme 2; dexamethasone; diarrhea; enteroendocrine cells; nausea; vomiting.
© 2020 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.