The Potential of Thyroid Hormone Therapy in Severe COVID-19: Rationale and Preliminary Evidence

Mourouzis, Iordanis; Apostolaki, Vassiliki; Trikas, Athanasios; Kokkinos, Leonidas; Alexandrou, Natassa; Avdikou, Maria; Giannoulopoulou, Myrto; Vassi, Aimilia; Tseti, Ioulia; Pantos, Constantinos

doi:10.3390/ijerph19138063

Cited by 5 publications

(6 citation statements)

References 81 publications

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“…The reduced generation of ROS and reduced induction of oxidative stress exerts, in fact, a protective role in the pathogenesis of the acute immunological damages caused by SARS-CoV-2 infection. Since the reduced levels of FT3 are associated with reduced oxidation, it is possible that the use of T3 treatment, proposed for the management of severe COVID-19 [ 77 ], could be responsible for an increase in oxidative stress. The use of antioxidants, such as N-acetylcysteine, proved to be effective against severe COVID-19 [ 78 ] and could be useful to mitigate such effects.…”

Section: Discussionmentioning

confidence: 99%

Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients

et al. 2022

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Background: Thyroid hormones (TH)s are master regulators of mitochondrial activity and biogenesis. Nonthyroidal illness syndrome (NTIS) is generally considered an adaptative response to reduced energy that is secondary to critical illness, including COVID-19. COVID-19 has been associated with profound changes in the cell energy metabolism, especially in the cells of the immune system, with a central role played by the mitochondria, considered the power units of every cell. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affects and alters mitochondrial functions, both to influence its intracellular survival and to evade host immunity. Aim of the study: This study was undertaken to analyze the oxidative balance and mitochondrial respiration in COVID-19 patients with and without NTIS to elucidate the role that thyroid hormones (TH)s play in this context. Methods: In our cohort of 54 COVID-19 patients, admitted to our University Hospital during the COVID-19 pandemic, we evaluated the generation of reactive oxygen species (ROS) by measuring the serum levels of derivatives of reactive oxygen metabolites (dROMs), and we analyzed the antioxidant capacity by measuring the serum biological antioxidant potential (BAP). We then analyzed the mitochondrial respiration in peripheral blood mononuclear cells (PBMC)s of 28 of our COVID-19 patients, using the seahorse instrument (Agilent). Results were correlated with the serum levels of THs and, in particular, of FT3. In addition, the role of T3 on bioelectrical impedance analysis (BIA) and mitochondrial respiration parameters was directly evaluated in two COVID-19 patients with NTIS, in which treatment with synthetic liothyronine (LT3) was given both in vivo and in vitro. Results: In our COVID-19 patients with NTIS, the dROMs values were significantly lower and the BAP values were significantly higher. Consequently, the oxidative stress index (OSi), measured as BAP/dROMs ratio was reduced compared to that observed in COVID-19 patients without NTIS, indicating a protective role exerted by NTIS on oxidative stress. In our COVID-19 patients, the mitochondrial respiration, measured in PBMCs, was reduced compared to healthy controls. Those with NTIS showed a reduced maximal respiratory capacity and a reduced proton leak, compared to those with normal FT3 serum values. Such lowered mitochondrial respiratory capacity makes the cells more vulnerable to bioenergetic exhaustion. In a pilot study involving two COVID-19 patients with NTIS, we could reinforce our previous observation regarding the role of T3 in the maintenance of adequate peripheral hydroelectrolytic balance. In addition, in these two patients, we demonstrated that by treating their PBMCs with LT3, both in vitro and in vivo, all mitochondrial respiration parameters significantly increased. Conclusions: Our results regarding the reduction in the serum levels of the reactive oxygen species (ROS) of COVID-19 patients with NTIS support the hypothesis that NTIS could represent an adaptative response to severe COVID-19. However, beside this beneficial effect, we demonstrate that, in the presence of an acute reduction of FT3 serum levels, the mitochondrial respiration is greatly impaired, with a consequent establishment of a hypoenergetic state of the immune cells that may hamper their capacity to react to massive viral infection.

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Section: Discussionmentioning

confidence: 99%

Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients

et al. 2022

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“…The clinical trial was registered in April 2020 (NCT04348513) and is listed as ‘terminated’ in September 2021 after enrolment of five patients. Some data from these patients was published, and the authors state the trial was ceased due to continuously changing treatment protocols for the management of COVID-19 [9].…”

Section: Coronavirus Disease 2019mentioning

confidence: 99%

The use of triiodothyronine during critical illness

Maiden,

Forehan

2024

Current Opinion in Clinical Nutrition &Amp; Metabolic Care

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Purpose of review Thyroid hormone physiology changes during critical illness. Circulating concentration of triiodothyronine (T3), the active form of thyroid hormone decreases. It has long been uncertain whether this represents a pathologic change or if it is an adaptive phenomenon. Controlled clinical trials have been required to understand whether replacing and restoring serum T3 levels is therapeutic. Recent findings Clinical trials of T3 have recently been proposed with some completed. These have been conducted in patients with sepsis, myocardial infarction, infants undergoing cardiac surgery, and acute respiratory distress syndrome. Of the completed trials, T3 administration restored serum concentrations, but was not accompanied by significant clinical benefit. Importantly, restoring serum T3 levels did not cause any adverse effects. Summary If T3 is to be considered a therapeutic target in critical illness, further studies should consider the stage of disease it is administered, and whether there are other surrogate measures to assess adequacy of hormone replacement over and above serum T3 concentrations.

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“…This NTIS pattern, albeit common, was related to the severity of critical illness rather than SARS-CoV-2 infection [ 27 ]. Tissue hypoxia is prominent in severe COVID-19; T3 may prevent this hypoxia and a relevant clinical trial has been initiated [ 28 ].…”

Section: Endocrine Aspects Of Sars-cov-2 Infectionmentioning

confidence: 99%

Endocrine Aspects of ICU-Hospitalized COVID-19 Patients

Diamantopoulos

Dimopoulou

Mourelatos

et al. 2022

JPM

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The unprecedented scale of the current SARS-CoV-2/COVID-19 pandemic has led to an extensive—yet fragmented—assessment of its endocrine repercussions; in many reports, the endocrine aspects of COVID-19 are lumped together in intensive care unit (ICU) patients and non-ICU patients. In this brief review, we aimed to present endocrine alterations in ICU-hospitalized patients with COVID-19. There are tangible endocrine disturbances that may provide fertile ground for COVID-19, such as preexisting diabetes. Other endocrine disturbances accompany the disease and more particularly its severe forms. Up to the time of writing, no isolated robust endocrine/hormonal biomarkers for the prognosis of COVID-19 have been presented. Among those which may be easily available are admission glycemia, thyroid hormones, and maybe (OH)25-vitamin D3. Their overlap among patients with severe and less severe forms of COVID-19 may be considerable, so their levels may be indicative only. We have shown that insulin-like growth factor 1 may have prognostic value, but this is not a routine measurement. Possibly, as our current knowledge is expanding, the inclusion of selected routine endocrine/hormonal measurements into artificial intelligence/machine learning models may provide further information.

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The Potential of Thyroid Hormone Therapy in Severe COVID-19: Rationale and Preliminary Evidence

Cited by 5 publications

References 81 publications

Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients

Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients

The use of triiodothyronine during critical illness

Endocrine Aspects of ICU-Hospitalized COVID-19 Patients

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