Serotonin is elevated in COVID-19-associated diarrhoea

Ha, Seeun; Jin, Byungchang; Clemmensen, Brooke; Park, Paul; Mahboob, Sumaiya; Gladwill, Vadim; Lovely, Farah Madhani; Gottfried-Blackmore, Andrés; Habtezion, Aida; Verma, Subhash C.; Ro, Seungil

doi:10.1136/gutjnl-2020-323542

Cited by 49 publications

(40 citation statements)

References 10 publications

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“…Interestingly, the 5-HT deficiency state in COVID-19, as suggested above, has been vindicated in a recent study [43], where it has been found that the 5-HT levels in coronavirus patients are indeed reduced though the researchers assumed [43] that the reduction of 5-HT may be due to the alteration in enterochromaffin cell functions or increased 5-HT degradation by monoamine oxidase (MAO, a family of enzymes where MAO-A is specifically involved in the process of breaking down of 5-HT to 5-hydroxyindoleacetic acid, 5-HIAA). In another study [44], an apparent increase in plasma 5-HT level in a specific case has been attributed to the possibility of delayed or insufficient breakdown of 5-HT to 5-HIAA in the liver, although, in such case, the brain 5-HT level (central 5-HT) should remain unaffected as 5-HT cannot cross the BBB.…”

Section: Second Does Anosmia Then Results From Coronavirus Induced Damage Of the Olfactory Neurons?mentioning

confidence: 97%

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

Sen¹

2021

Preprint

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Anosmia, ageusia and impaired chemesthetic sensations are quite common in coronavirus patients. Different mechanisms have been proposed to explain the anosmia and ageusia of COVID-19 patients, though for reversible anosmia and ageusia, which are resolved quickly, the proposed mechanisms seem to be incomplete. In addition, the reason behind the impaired chemesthetic sensations of some coronavirus patients remains unknown. It is proposed that in coronavirus patients, there is depletion of tryptophan (an essential amino acid), as ACE2, a key element in the process of absorption of tryptophan from food, is significantly reduced due to the attack of coronavirus which use ACE2 as the receptor for its entry into the host cells. Incidentally, the depletion of tryptophan should lead to deficiency of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency not only explains fast resolved anosmia and ageusia, but also dysfunctional chemesthesis, given the fact that 5-HT is an important neuromodulator in the olfactory neurons and taste receptor cells and 5-HT also enhances the nociceptor activity of transient receptor potential channels (TRP channels) responsible for chemesthetic sensations. The female predominance of olfactory and gustatory dysfunctions can also be explained by considering low 5-HT levels in women. In addition, 5-HT deficiency worsens silent hypoxemia and explains why hypoxic pulmonary vasoconstriction is nearly absent in coronavirus patients leading to poor outcome. Hence, clinical trials should be conducted on coronavirus patients to find out how different selective serotonin reuptake inhibitors (SSRIs) and serotonin agonists work out in eliminating or improving the olfactory, gustatory and chemesthetic dysfunctions as well as hypoxemia.

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Section: Second Does Anosmia Then Results From Coronavirus Induced Damage Of the Olfactory Neurons?mentioning

confidence: 97%

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

Sen¹

2021

Preprint

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“…Serotonin is an endogenous signalling molecule involved in the regulation of fluid and mucus secretion as well as regulation of ion transport in gastrointestinal tract (Banskota et al 2019) capable of altering intestinal motility and implicated in diarrhoea outcome (Thiagarajah et al 2015;Camilleri et al 2017;Hu and Spencer 2018). In fact, several diarrhoeagenic agents have been strongly related to this molecule (Ha et al 2021;Westerberg et al 2018;Singhal et al 2017). Serotonin effects are achieved through the action on epithelial 5-HT 2 receptor and neuronal 5-HT 1 , 5-HT 3 and 5-HT 4 receptors (Fidalgo et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Serotonin involvement in okadaic acid-induced diarrhoea in vivo

et al. 2021

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The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms including nausea, vomiting and diarrhoea. These phycotoxins are Ser/Thr phosphatase inhibitors, which produce hyperphosphorylation in cellular proteins. However, this inhibition does not fully explain the symptomatology reported and other targets could be relevant to the toxicity. Previous studies have indicated a feasible involvement of the nervous system. We performed a set of in vivo approaches to elucidate whether neuropeptide Y (NPY), Peptide YY (PYY) or serotonin (5-HT) was implicated in the early OA-induced diarrhoea. Fasted Swiss female mice were administered NPY, PYY(3–36) or cyproheptadine intraperitoneal prior to oral OA treatment (250 µg/kg). A non-significant delay in diarrhoea onset was observed for NPY (107 µg/kg) and PYY(3–36) (1 mg/kg) pre-treatment. On the contrary, the serotonin antagonist cyproheptadine was able to block (10 mg/kg) or delay (0.1 and 1 mg/kg) diarrhoea onset suggesting a role of 5-HT. This is the first report of the possible involvement of serotonin in OA-induced poisoning.

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“…It has been postulated that SARS-CoV-2 might have an indirect effect on enteroendocrine cells (EEC), triggering the release of neuroactive agents such as the emesis inducing serotonin [14]. Most studies showed that patients with COVID-19 have higher plasma serotonin levels and this correlates with increased IL-6 [15,16], while others concluded they have decreased serotonin levels [17]. Considering serotonin's role in regulating innate and adaptive immune responses [18], the observed beneficial effect of ondansetron might be due to the modulation of serotonin levels or could also be linked with a direct effect on the immune system [19] or on known COVID-19 comorbidities, such liver and kidney disease or complications, such as thrombosis [20][21][22].…”

Section: Discussionmentioning

confidence: 99%

Ondansetron use is associated with lower COVID-19 mortality in a Real-World Data network-based analysis

Miller

Ellis

Sarangarajan

et al. 2021

Preprint

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Objective: The COVID-19 pandemic generated a massive amount of clinical data, which potentially holds yet undiscovered answers related to COVID-19 morbidity, mortality, long term effects, and therapeutic solutions. The objective of this study was to generate insights on COVID-19 mortality-associated factors and identify potential new therapeutic options for COVID-19 patients by employing artificial intelligence analytics on real-world data. Materials and Methods: A Bayesian statistics-based artificial intelligence data analytics tool (bAIcis®) within Interrogative Biology® platform was used for network learning, inference causality and hypothesis generation to analyze 16,277 PCR positive patients from a database of 279,281 inpatients and outpatients tested for SARS-CoV-2 infection by antigen, antibody, or PCR methods during the first pandemic year in Central Florida. This approach generated causal networks that enabled unbiased identification of significant predictors of mortality for specific COVID-19 patient populations. These findings were validated by logistic regression, regression by least absolute shrinkage and selection operator, and bootstrapping. Results: We found that in the SARS-CoV-2 PCR positive patient cohort, early use of the antiemetic agent ondansetron was associated with increased survival in mechanically ventilated patients. Conclusions: The results demonstrate how real world COVID-19 focused data analysis using artificial intelligence can generate valid insights that could possibly support clinical decision-making and minimize the future loss of lives and resources.

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Serotonin is elevated in COVID-19-associated diarrhoea

Cited by 49 publications

References 10 publications

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

Serotonin involvement in okadaic acid-induced diarrhoea in vivo

Ondansetron use is associated with lower COVID-19 mortality in a Real-World Data network-based analysis

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