Pineal hormone melatonin as an adjuvant treatment for COVID‑19 (Review)

Vlachou, Marilena; Siamidi, Angeliki; Dedeloudi, Aikaterini; Konstantinidou, Sofia K.; Papanastasiou, Ioannis

doi:10.3892/ijmm.2021.4880

Cited by 30 publications

(27 citation statements)

References 70 publications

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“…Incidentally, 5-HT is the precursor in the synthesis of pineal and extrapineal melatonin ( Fig. 1 ), which is well-known as a chronobiotic, hypnotic, neuroprotective and cardioprotective agent, and, of late, melatonin has been touted as a potential adjuvant in the fight against COVID-19 because of its immunomodulatory, anti‑inflammatory and anti‑oxidative effects [111] , [112] . Consequently, 5-HT deficiency should lead to a reduction of melatonin putting the coronavirus patients at a further disadvantage.…”

Section: Implications and Importance Of The Hypothesismentioning

confidence: 99%

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

Sen¹

2021

Medical Hypotheses

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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.

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Section: Implications and Importance Of The Hypothesismentioning

confidence: 99%

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

Sen¹

2021

Medical Hypotheses

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“…In order to measure antibody titers [immunoglobulin (Ig)A, IgM and IgG], serological tests on whole blood, serum, plasma or saliva are usually performed. Some of these are qualitative, while others are semi-quantitative and others quantitative ( 11 , 17 , 18 ). The present study utilized semi-quantitative ELISA in order to evaluate IgG titers in the serum of vaccinated individuals who have received two doses of the BNT162b2 COVID-19 mRNA vaccine.…”

Section: Introductionmentioning

confidence: 99%

Immune response (IgG) following full inoculation with BNT162b2 COVID‑19 mRNA among healthcare professionals

et al. 2021

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Soon after the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in December, 2019, numerous research teams, assisted by vast capital investments, achieved vaccine development in a fraction of time. However, almost 8 months following the initiation of the European vaccination programme, the need for prospective monitoring of the vaccine-induced immune response, its determinants and related side-effects remains a priority. The present study aimed to quantify the immune response following full vaccination with the BNT162b2 coronavirus disease 2019 (COVID-19) mRNA vaccine by measuring the levels of immunoglobulin G (IgG) titers in healthcare professionals. Moreover, common side-effects and factors associated with IgG titers were identified. For this purpose, blood samples from 517 individuals were obtained and analysed. Blood sampling was performed at a mean period of 69.0±23.5 days following the second dose of the vaccine. SARS-CoV-2 IgG titers had an overall mean value of 4.23±2.76. Females had higher titers than males (4.44±2.70 and 3.89 ±2.84, respectively; P=0.007), while non-smokers had higher titers than smokers (4.48±2.79 and 3.80±2.64, respectively; P=0.003). An older age was also associated with lower antibody titers (P<0.001). Moreover, the six most prevalent adverse effects were pain at the injection site (72.1%), generalized fatigue (40.5%), malaise (36.3%), myalgia (31,0%), headache (25.8%) and dizziness/weakness (21.6%). The present study demonstrated that the immune response after receiving the BNT162b2 COVID-19 mRNA vaccine is dependent on various modifiable and non-modifiable factors. Overall, the findings of the present study highlight two key aspects of the vaccination programs: First, the need for prospective immunosurveillance studies in order to estimate the duration of immunity, and second, the need to identify those individuals who are at a greater risk of developing low IgG titers in order to evaluate the need for a third dose of the vaccine.

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“…Similar role of 5-HT in high-altitude silent hypoxemia cannot be ruled out given the fact that high altitude lowers 5-HT production as explained earlier [64,65]. Furthermore, 5-HT is the precursor in the synthesis of pineal and extrapineal melatonin, which is well-known as a chronobiotic, hypnotic, neuroprotective and cardioprotective agent, and, of late, melatonin has been touted as a potential adjuvant in the fight against COVID-19 because of its immunomodulatory, anti-inflammatory and anti-oxidative effects [111,112].…”

Section: Second Does Anosmia Then Results From Coronavirus Induced Damage Of the Olfactory Neurons?mentioning

confidence: 97%

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

Sen¹

2021

Preprint

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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.

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Pineal hormone melatonin as an adjuvant treatment for COVID‑19 (Review)

Cited by 30 publications

References 70 publications

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

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

Immune response (IgG) following full inoculation with BNT162b2 COVID‑19 mRNA among healthcare professionals

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

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