COVID‐19, nausea, and vomiting

Abstract

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.

Persistent Brainstem Dysfunction in Long-COVID: A Hypothesis

“…While receiving afferent neurons from the gastrointestinal tract, the NTS also has neural connections to higher-order brain areas (e.g., amygdala, insula, and anterior cingulate cortex), which may convey nausea sensation. 92 , 93 …”

Mechanisms of Nausea and Vomiting: Current Knowledge and Recent Advances in Intracellular Emetic Signaling Systems

“…Both angiotensin-converting enzyme 2 and the cellular serine protease transmembrane protease serine-2 are required for viral entry, which are expressed in upper gastrointestinal tract enterocytes. The angiotensin 2 converting enzyme is expressed on enteroendocrine cells, and SARS–CoV-2 infects enterocytes but not enteroendocrine cells (studies needed with native enteroendocrine cells) [ 219 ]. The subsequent virus-evoked release of epithelial emetic mediators via exocytosis, inflammation, and apoptosis may trigger the intestinal and brainstem emetic drives.…”

“…Moreover, SARS–CoV-2 increases plasma angiotensin II levels, which is a centrally (area postrema) acting emetic agent, thus providing an additional mechanism for COVID-19-evoked emesis. Viral invasion of the dorsal brainstem can be also a possibility, but more likely during delayed onset symptoms [ 219 ].…”

Decision on Chemotherapy Amidst COVID-19 Pandemic: a Review and a Practical Approach from Iran

“…(3) nausea and vomiting: N/V are the early symptom of COVID-19 [ 23 ]. To differentiate it from the CTx-induced N/V (CINV), the physician needs to consider the emetogenicity of CTx agents, and other risk factors of CINV including female gender, young age, history of N/V with prior CTx cycles [ 20 ].…”

“…To differentiate it from the CTx-induced N/V (CINV), the physician needs to consider the emetogenicity of CTx agents, and other risk factors of CINV including female gender, young age, history of N/V with prior CTx cycles [ 20 ]. The most clinically relevant neurotransmitters involved in COVID-19-induced N/V are serotonin, substance P, and cholecystokinin, while CINV is mainly mediated by serotonin, dopamine, substance P, and cannabinoids [ 20 23 ]. Considering almost common mediators, the management of N/V - in either case - is similar and includes the combination of a serotonin antagonist ( e.g.…”