COVID-19 and Diarrhoea: the Therapeutic Role OF LMWH.

Dear Editor,

We read with great interest the paper by Ghimire S et al. [1] demonstrating that diarrhoea in COVID-19 is related to a worse prognosis. Furthermore, the authors confirmed that it is the most common gastrointestinal symptom related to SARS-COV-2 infection.

How to treat diarrhoea is not still clear; however, the therapeutic role of low molecular weight heparin (LMWH) should be underlined because it is based on pathophysiological principles.

On one hand, an association between diarrhoea in COVID-19 and increased level of serotonin (5-HT) has been recently demonstrated [2], and it is widely known that 5-HT stimulates platelet aggregation [3] and consequently increases the risk of micro and macro-thrombosis, worsening the prognosis of the disease.

On the other hand, diarrhoea in COVID-19 seems to be related to both direct and indirect mucosal damage: the direct damage may be due to the disruption of the tight-junctions by SARS-COV-2 itself [4], and the indirect effect can be caused by the systemic inflammatory response and the ischemic damage of enterocytes [4]. This mucosal damage may increase the bacterial translocation through the intestinal wall.

That contributes to the persistence of diarrhoea and can cause a bacterial systemic superinfection: IL-6, a fundamental pathogenetic cytokine for COVID-19 severity but also a biomarker of inflammation associated with endotoxemia and sepsis [5], achieved high levels in patients with diarrhoea [2].

Furthermore, the associated damage of enterochromaffin cells and intrinsic enteric neurons can increase the release of circulating 5-HT, establishing a vicious circle [3].

LMWH acts on these pathogenetic mechanisms.

On one side, it decreases systemic and local platelet aggregation interfering with the hypercoagulable state induced by 5-HT [3]; on the other side, it improves intestinal microcirculation able to decrease enterocytic damage and therefore bacterial translocation [5].

For these reasons, LMWH represents the proper therapy for diarrhoea in COVID-19 patients and, so on, contributes to improve the prognosis.