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

Abstract

Different mechanisms forwarded to understand anosmia and ageusia in coronavirus patients are not adequate to explain reversible anosmia and ageusia, which are resolved quickly. In addition, the reason behind the impaired chemesthetic sensations in some coronavirus patients remains unknown. In the present paper it is proposed that SARS-CoV-2 patients suffer from depletion of tryptophan, as ACE2, a key element in the process of absorption of tryptophan from the food, is significantly reduced in the patients as coronavirus uses ACE2 as the receptor to enter the host cells. The tryptophan depletion leads 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 explain anosmia, ageusia and dysfunctional chemesthesis in COVID-19, given the fact that 5-HT is an important neuromodulator in the olfactory neurons, taste receptor cells and transient receptor potential channels (TRP channels) involved in chemesthesis. In addition, 5-HT deficiency worsens silent hypoxemia and depresses hypoxic pulmonary vasoconstriction leading to increased severity of the disease. Also, the levels of anti-inflammatory melatonin (synthesized from 5-HT) and nicotinamide adenine dinucleotide (NAD + , produced from niacin whose precursor is the tryptophan) might decrease in coronavirus patients resulting in the aggravation of the disease. Interestingly, selective serotonin reuptake inhibitors (SSRIs) may not be of much help in correcting the 5-HT deficiency in COVID-19 patients, as their efficacy goes down significantly when there is depletion of tryptophan in the system. Hence, tryptophan supplementation may herald a radical change in the treatment of COVID-19 and accordingly, clinical trials (therapeutic / prophylactic) should be conducted on coronavirus patients to find out how tryptophan supplementation (oral or parenteral, the latter in severe cases where there is hardly any absorption of tryptophan from the food) helps in curing, relieving or preventing the olfactory, gustatory and chemesthetic dysfunctions and in lessening the severity of the disease.

Ongoing Use of SSRIs Does Not Alter Outcome in Hospitalized COVID-19 Patients: A Retrospective Analysis

“…Anti-inflammatory effects of SSRIs may thus underlie their possible protective role in COVID-19 [ 11 ]. Serotonin may have a direct effect on the immune system and COVID-19 may induce serotonin deficiency [ 20 , 21 ]. An example of serotonin’s effect on the immune system is seen in T lymphocytes where SSRIs decrease their viability and immunoreactive protein content [ 22 ].…”

Mechanisms and clinical evidence to support melatonin's use in severe COVID-19 patients to lower mortality

“…However, ACE2 is a key element in the process of absorption of tryptophan, the necessary precursor of melatonin. When the ACE2 is occupied by SARS-CoV2, it leads to tryptophan depletion as well as a likely melatonin deficiency in COVID-19 patients [69] . Also, melatonin may serve as an indirect regulator of ACE2 via binding to calmodulin [70] or by impacting MMP9 [71] ; both calmodulin and MMP9 directly modulate the ACE2 activity.…”

The relationship between the serotonergic system and COVID-19 disease: A review

“…A group of researchers have previously claimed that the body's tryptophan is depleted among COVID-19 patients due to the decreased ACE 2 , which plays a key role in tryptophan absorption from food. In this regard, tryptophan is a precursor to the synthesis of 5-HT and its depletion consequently leads to a defect in the production of 5-HT, which is known as an important neuromodulator in olfactory neurons and taste buds, so that smell and taste senses may be lost in most COVID-19 patients [ 64 ].…”