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

Abstract

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.