Thyroid hormone levels during hospital admission inform disease severity and mortality in COVID-19 patients

Beltrão, Fabyan Esberard de Lima; Beltrão, Daniele Carvalhal de Almeida; Cordeiro, Giulia Carvalhal de Almeida; Beltrão, Fabricia Elizabeth de Lima; Brito, Amanda da Silva; Capistrano, Kamilla Helen Rodrigues; Bastos, Isis Henriques de Almeida; Hecht, Fabio; Daltro, Carla Hilário da Cunha; Bianco, Antonio Carlos; Gonçalves, Maria da Conceição Rodrigues; Ramos, Helton Estrela

INTRODUCTION: Illness severity in patients infected with COVID-19 is variable. METHODS: Here we conducted an observational, longitudinal, and prospective cohort study to investigate serum thyroid hormone levels (TH) in adult COVID-19 patients, admitted between June and August 2020, and to determine whether they reflect the severity or mortality associated with the disease. RESULTS: 245 patients [median age: 62 (49-75) years] were stratified in non-critical (181) and critically ill (64). 58 patients (23.6 %) were admitted to the ICU and 41 (16.7%) died. 16 (6.5%) exhibited isolated low levels of fT3. fT3 levels were lower in critically ill compared to non-critical patients [fT3: 2.82 (2.46- 3.29) vs 3.09 (2.67-3.63) pg/mL, P=0.007]. Serum rT3 was mostly elevated but less so in critically ill compared to non-critical patients [rT3: 0.36 (0.28- 0.56) vs 0.51(0.31-0.67) ng/mL, P=0.001]. The univariate logistic regression revealed correlation between in-hospital mortality and serum fT3 levels (OR: 0.47; 95% CI: 0.29-0.74; P=0.0019), rT3 levels (OR: 0.09; 95% CI: 0.01-0.49; P=0.006) and the product fT3●rT3 (OR: 0.47; 95% CI: 0.28-0.74; P=0.0026). Serum TSH, fT4, and fT3/rT3 values were not significantly associated with mortality and severity of the disease. A serum cutoff level of fT3 (≤ 2.6 pg/mL) and rT3 (≤0.38 ng/mL) were associated with 3.46 and 5.94 OR of mortality, respectively. The Area Under the ROC curve (AUC) for serum fT3 (AUC=0.66), rT3 (AUC=0.64), and the product of serum fT3●rT3 (AUC=0.70). NTIS (fT3 < 2.0 pg/mL) was associated with a 7.05 OR of mortality (95% CI: 1.78-28.3, P=0.005) and the product rT3●fT3 ≤ 1.29 with an 8.08 OR of mortality (95% CI: 3.14-24.2, P<0.0001). CONCLUSION: This prospective study reports data on the largest number of hospitalized moderate-to-severe COVID-19 patients and correlates serum TH levels with illness severity, mortality, and other biomarkers to critical illness. The data revealed the importance of early assessment of thyroid function in hospitalized patients with COVID-19, given the good prognostic value of serum fT3, rT3 and fT3•rT3 product. Further studies are necessary to confirm these observations.