PMID- 36290721 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221030 IS - 2076-3921 (Print) IS - 2076-3921 (Electronic) IS - 2076-3921 (Linking) VI - 11 IP - 10 DP - 2022 Oct 8 TI - Opposite Effect of Thyroid Hormones on Oxidative Stress and on Mitochondrial Respiration in COVID-19 Patients. LID - 10.3390/antiox11101998 [doi] LID - 1998 AB - 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. FAU - De Vitis, Claudia AU - De Vitis C AUID- ORCID: 0000-0001-8899-2347 AD - Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy. FAU - Capalbo, Carlo AU - Capalbo C AUID- ORCID: 0000-0001-8445-6782 AD - Department of Medical Oncology, Sant'Andrea University Hospital, 00189 Rome, Italy. AD - Department of Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy. FAU - Torsello, Alessandra AU - Torsello A AD - Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy. FAU - Napoli, Christian AU - Napoli C AUID- ORCID: 0000-0002-5775-2276 AD - Department of Surgical and Medical Science and Translational Medicine, Sapienza University of Rome, 00181 Rome, Italy. FAU - Salvati, Valentina AU - Salvati V AD - Scientific Direction, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy. FAU - Loffredo, Chiara AU - Loffredo C AD - Unit of Anesthesia, Intensive Care and Pain Medicine, Sant'Andrea University Hospital, 00189 Rome, Italy. FAU - Blandino, Giovanni AU - Blandino G AD - Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy. FAU - Piaggio, Giulia AU - Piaggio G AD - UOSD SAFU, Department of Research, Diagnosis and Innovative Technologies, IRCCS Regina Elena National Cancer Institute, 00144 Roma, Italy. FAU - Auciello, Francesca Romana AU - Auciello FR AD - Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy. FAU - Pelliccia, Flaminia AU - Pelliccia F AD - Unit of Anesthesia, Intensive Care and Pain Medicine, Sant'Andrea University Hospital, 00189 Rome, Italy. FAU - Salerno, Gerardo AU - Salerno G AUID- ORCID: 0000-0002-6597-1452 AD - Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy. FAU - Simmaco, Maurizio AU - Simmaco M AD - Department of Neuroscience, Mental Health, and Sensory Organs (NESMOS), Sapienza University of Rome, 00189 Rome, Italy. FAU - Di Magno, Laura AU - Di Magno L AUID- ORCID: 0000-0001-9446-8752 AD - Department of Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy. FAU - Canettieri, Gianluca AU - Canettieri G AUID- ORCID: 0000-0001-6694-2613 AD - Department of Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy. AD - Pasteur Institute, Cenci-Bolognetti Foundation, 00161 Rome, Italy. FAU - Coluzzi, Flaminia AU - Coluzzi F AUID- ORCID: 0000-0001-7184-5519 AD - Unit of Anesthesia, Intensive Care and Pain Medicine, Sant'Andrea University Hospital, 00189 Rome, Italy. AD - Department Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, 04100 Latina, Italy. FAU - Mancini, Rita AU - Mancini R AD - Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy. FAU - Rocco, Monica AU - Rocco M AUID- ORCID: 0000-0001-8380-3607 AD - Department of Surgical and Medical Science and Translational Medicine, Sapienza University of Rome, 00181 Rome, Italy. AD - Unit of Anesthesia, Intensive Care and Pain Medicine, Sant'Andrea University Hospital, 00189 Rome, Italy. FAU - Sciacchitano, Salvatore AU - Sciacchitano S AUID- ORCID: 0000-0003-1492-5365 AD - Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189 Rome, Italy. LA - eng PT - Journal Article DEP - 20221008 PL - Switzerland TA - Antioxidants (Basel) JT - Antioxidants (Basel, Switzerland) JID - 101668981 PMC - PMC9598114 OTO - NOTNLM OT - COVID-19 OT - bioelectrical impedance analysis (BIA) OT - biological antioxidant potential (BAP) OT - extracellular flux analyzer OT - mitochondrial respiration OT - nonthyroidal illness syndrome (NTIS) OT - oxidative stress OT - reactive oxygen species (ROS) OT - thyroid hormones (THs) COIS- There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. EDAT- 2022/10/28 06:00 MHDA- 2022/10/28 06:01 PMCR- 2022/10/08 CRDT- 2022/10/27 01:07 PHST- 2022/08/20 00:00 [received] PHST- 2022/10/03 00:00 [revised] PHST- 2022/10/04 00:00 [accepted] PHST- 2022/10/27 01:07 [entrez] PHST- 2022/10/28 06:00 [pubmed] PHST- 2022/10/28 06:01 [medline] PHST- 2022/10/08 00:00 [pmc-release] AID - antiox11101998 [pii] AID - antioxidants-11-01998 [pii] AID - 10.3390/antiox11101998 [doi] PST - epublish SO - Antioxidants (Basel). 2022 Oct 8;11(10):1998. doi: 10.3390/antiox11101998.