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Serotonin is elevated in COVID-19-associated diarrhoea
  1. Seeun Ha1,
  2. Byungchang Jin1,
  3. Brooke Clemmensen1,
  4. Paul Park1,
  5. Sumaiya Mahboob2,
  6. Vadim Gladwill2,
  7. Farah Madhani Lovely3,
  8. Andres Gottfried-Blackmore4,
  9. Aida Habtezion4,
  10. Subhash Verma5,
  11. Seungil Ro1
  1. 1 Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, USA
  2. 2 Internal Medicine, University of Nevada School of Medicine, Reno, Nevada, USA
  3. 3 Pulmonary and Critical Care Medicine, Renown Health, Reno, Nevada, USA
  4. 4 Gastroenterology and Hepatology, Stanford University Department of Medicine, Stanford, California, USA
  5. 5 Microbiology and Immunology, University of Nevada School of Medicine, Reno, Nevada, USA
  1. Correspondence to Dr Seungil Ro, Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557-0046, USA; sro{at}

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We read with great interest the recent publication by Lin et al,1 which reported diarrhoea as the most common GI symptom in patients with COVID-19. Diarrhoea as a symptom of COVID-19 has been commonly observed,2 3 but the cause remains unknown.

Diarrhoea occurs from excessive production of serotonin (5-hydroxytryptamine, 5-HT) in the GI tract.4 Ninety-five per cent of 5-HT is produced and released from the enterochromaffin cells within the epithelium of the GI tract. 5-HT localised to the GI tract is a key modulator of GI peristalsis.5 We hypothesised that plasma 5-HT levels are increased in patients with COVID-19 with diarrhoea.

Table 1 summarises the COVID-19 severity, interleukin 6 (IL-6), IgM/IgG antibodies, fever, GI symptoms, plasma 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), underlying diabetes, body mass index, gender and age measured in 80 patients with COVID-19 (10 patients with diarrhoea) and 18 healthy donors (see online supplemental material). Correlation analysis identified 5-HT, 5-HIAA and IL-6 as the most noticeable features in the COVID-19 cohort with diarrhoea. Patients with COVID-19 had significantly increased plasma 5-HT and 5-HIAA levels compared with healthy donors (figure 1A,D). When patients were categorised by disease severity, 5-HT and 5-HIAA levels increased with higher severity of symptoms (figure 1B,E). Patients with COVID-19 with diarrhoea had substantially higher 5-HT and 5-HIAA levels compared with patients without diarrhoea and the healthy group (table 1 and …

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  • SH and BJ contributed equally.

  • Contributors SH, BJ and SR designed the research. SH, BJ and SR analysed and generated the data. PP, SM, VG, FML, AG-B and AH obtained and analysed COVID-19 and healthy donor blood samples and clinical data. SH, BJ, BC and SR wrote the paper. SR revised the paper. All authors have approved the final version of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.