Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19? Amarnath Sen 40 Jadunath Sarbovouma Lane, Kolkata 700035, India, E-mail:
[email protected] ABSTRACT Anosmia, ageusia and impaired chemesthetic sensations are quite common in coronavirus patients. Different mechanisms have been proposed to explain the anosmia and ageusia in COVID-19, 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 in some coronavirus patients remains unknown. It is proposed that coronavirus patients suffer from depletion of tryptophan (an essential amino acid), as ACE2, a key element in the process of absorption of tryptophan from the food, is significantly reduced due to the attack of coronavirus, which use ACE2 as the receptor for its entry into the host cells. The depletion of tryptophan should lead to a deficit of serotonin (5-HT) in SARS-COV- 2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency can give rise to anosmia, ageusia and dysfunctional chemesthesis in COVID-19, 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 the chemesthetic sensations. In addition, 5-HT deficiency is expected to worsen silent hypoxemia and depress hypoxic pulmonary vasoconstriction (a protective reflex) leading to an increased severity of the disease and poor outcome. Melatonin, a potential adjuvant in the treatment of COVID-19, which can tone down cytokine storm, is produced from 5-HT and is expected to decrease due to the deficit of 5-HT in the coronavirus patients.