Bioelectrical Impedance Analysis (BIA) to measure alterations on hydroelectrolytic equilibrium of peripheral cells in COVID-19 patients with nonthyroidal illness syndrome (NTIS)

In COVID-19 patients the occurrence of low T3 serum values is associated with disease severity and death, but hormonal substitutive replacement is still debated. Clinical trials reported so far failed to demonstrate clear beneficial effects of T3, T4 or both treatments. With the aim to analyze the peripheral effects of the acute deficiency of T3 in blood, we analyzed body fluid composition in 74 COVID-19 patients, admitted to our University Hospital during the last pandemic wave. COVID-19 patients were sub divided into those that presented low FT3 serum levels, i.e.,  1.7 pg/ml (n. 42), 13 of which showed very low FT3 serum values, i.e.,  1.1 pg/ml, and those that showed normal FT3 serum levels, i.e., > 1.7 pg/ml (n. 32). Body fluid composition was analyzed by Bioelectrical Impedance Analysis (BIA). We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio, an indicator of the fraction of FFM as water and one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In conclusion, we demonstrated that the acute T3 deficit in our COVID-19 patients has marked effects on the hydroelectrolytic equilibrium of their peripheral blood mononuclear cells. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in these patients. Measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU that develop NTIS and may represent a novel reliable outcome to evaluate the benefit of T3 treatment in future clinical interventional trials.