Nonthyroidal illness syndrome (NTIS) in severe COVID-19 patients: role of T3 on the Na/K pump gene expression and on hydroelectrolytic equilibrium.

BACKGROUND: Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. METHODS AND FINDINGS: We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. 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. This ratio is an indicator of the fraction of FFM as water and represents 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). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. 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 addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. CONCLUSIONS: In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.

COVID-19 After Lung Resection in Northern Italy.

We reviewed surgical cases from 4 Thoracic Surgery departments in the Lombardia region of Italy, the area mostly affected by Coronavirus pandemic in Europe, with the aim to describe the impact of COVID-19 on the treatment of thoracic surgical patients. Clinical, radiological and laboratory data from patients who underwent lung resection from December 2019 to March 2020 were retrospectively collected until June 2020. Univariable Cox regression models were estimated to evaluate potential prognostic factors for developing COVID-19 and to investigate postoperative mortality among patients who developed symptomatic COVID-19 infection. We examined data from 107 patients. (74 lobectomies, 32 wedge/segmentectomies and 1 pneumonectomy). Twelve patients developed COVID-19 (Group 1), whereas 95 patients were not infected (Group 2). In Group 1, 6 patients (50%) died from complications related to infection; in Group 2, one patient (1%) died because of non-COVID-19-related causes. Median days from surgery to first symptoms, CT confirmation, clinical confirmation and PCR positivity was 48.1, 54.3, 55.1, and 55.2 respectively. At univariable analysis, DLCO/VA% (P = 0.008), duration of the surgery (P = 0.009), smoking history (pack/year) (P < 0.001), BMI (P< 0.001) and number of segments resected (P = 0.010) were associated with COVID-19 onset. Moreover, CCI (P < 0.001), DLCO/VA% (P = 0.002), cigarette pack/year (P < 0.001), BMI (P < 0.001) and COVID-19 (P < 0.001) were associated with death. Patients who undergo lung resection and then develop symptomatic COVID-19 infection are at higher risk of developing severe respiratory complications and postoperative death. Insidious symptoms' onset may lead to a delay in diagnosis. We suggest two mitigating strategies: (1) Improve symptoms surveillance and isolation during recovery period, (2) Be aware of a potential greater risk of developing symptomatic COVID-19 and death correlated with elevated CCI, BMI, smoking history, DLCO/VA%, number of resected segments and duration of surgery.