COVID-19 Pathophysiology: Are Platelets and Serotonin Hiding in Plain Sight?

22 Pages Posted: 18 Mar 2021

See all articles by Farid Jalali

Farid Jalali

Saddleback Medical Group

Salim Rezaie

CIUSSS EMTL

Philippe Rola

Greater San Antonio Emergency Physicians (GSEP)

Cameron Kyle-Sidell

Maimonides Medical Center - Department of Emergency Medicine

Date Written: February 5, 2021

Abstract

Established evidence suggests that in ARDS, platelets may exhibit a dysregulated state that exacerbates lung injury. We review evidence that suggests this platelet-mediated lung injury, while present in ARDS in general, is amplified in COVID-19 ARDS in particular. Driven by a quantifiably higher degree of platelet activation and ensuing platelet serotonin liberation into plasma compared to ARDS of other etiologies, the plasma serotonin excess in COVID-19 may be responsible for many of the devastating pulmonary and extra-pulmonary clinical manifestations of the severe disease. There is ample evidence and biologic plausibility to suggest that effective serotonin receptor (5HT-2) antagonism may reverse serotonin-mediated pulmonary vasoconstriction, lessen pulmonary platelet trapping, inhibit platelet activation and aggregation, normalize increased respiratory drive, mitigate risk of pulmonary fibrosis, and counteract adverse renal, neurologic, and cardiovascular phenomena in severe COVID-19. Given we have a well-tolerated, safe, and inexpensive oral 5HT-2 antagonist, cyproheptadine, we hope to build consensus for the need to urgently investigate 5HT-2 receptor antagonism as a treatment option for severe COVID-19.

Note: Funding Statement: No funding was obtained for the submitted manuscript and the work that went into synthesizing this paper.

Declaration of Interests: All authors declare no competing interests.

Keywords: COVID, COVID-19, Serotonin, Platelet, ARDS

Suggested Citation

Jalali, Farid and Rezaie, Salim and Rola, Philippe and Kyle-Sidell, Cameron, COVID-19 Pathophysiology: Are Platelets and Serotonin Hiding in Plain Sight? (February 5, 2021). Available at SSRN: https://ssrn.com/abstract=3800402 or http://dx.doi.org/10.2139/ssrn.3800402

Farid Jalali (Contact Author)

Saddleback Medical Group ( email )

United States

Salim Rezaie

CIUSSS EMTL ( email )

Canada

Philippe Rola

Greater San Antonio Emergency Physicians (GSEP) ( email )

United States

Cameron Kyle-Sidell

Maimonides Medical Center - Department of Emergency Medicine ( email )

United States

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