Among hospitalized patients with COVID-19, an elevation of serum reverse triiodothyronine (rT3) levels was the most frequently observed change (∼63%), followed by high serum elevated free thyroxine (fT4) levels (∼21%) and low serum thyrotropin (TSH) levels (∼7.3%), researchers reported in Thyroid.

The observational, longitudinal, prospective cohort study assessed thyroid hormone levels and their association with serum proinflammatory biomarkers and COVID-19–associated severity and mortality. A total of 245 patients hospitalized with confirmed COVID-19 infection at a tertiary referral hospital in Brazil from June 2020 to August 2020 were enrolled.

The enrolled patients were median aged 62 years (range, 49-74.5) and 145 patients (59.1%) were men. The average hospital stay was 8.3 days. During that time 58 patients (23.6%) were admitted to the intensive care unit, 41 (16.7%) of whom later died. Patients were categorized as noncritically ill (n = 181) and critically ill (n = 64) within 48 hours of hospital admission.


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Of the full cohort of 245 patients, 16 (∼6.5%) had nonthyroidal illness syndrome (NTIS) with isolated low levels of free triiodothyronine (fT3). Critically ill patients had lower fT3 levels compared with noncritically patients (2.82 [2.46-3.29] pg/mL vs 3.09 [2.67-3.63] pg/mL, respectively, P = .007). Serum reverse triiodothyronine (rT3) was  somewhat elevated but to a lesser degree in critically ill patients compared with the level in noncritically ill patients (0.36 [0.28-0.56] ng/mL vs 0.51 [0.31-0.67] ng/mL, respectively, P  = .001).

Univariate logistic regression analysis demonstrated a correlation between in-hospital mortality and serum fT3 levels (odds ratio [OR] 0.47; 95% CI, 0.29-0.74; P = .0019), rT3 levels (OR 0.09; CI, 0.01-0.49; P  = .006), and the product fT3 × rT3 (OR 0.47; CI, 0.28-0.74; P  = .0026). Serum thyrotropin, free thyroxine, and fT3/rT3 levels were not significantly associated with mortality or disease severity.

Analysis with area under the receiver operating characteristic (ROC) and area under the curve (AUC) score showed 3 COVID-19 mortality predictors: serum fT3 (AUC = 0.66), rT3 (AUC = 0.64), and the product of serum fT3 × rT3 (AUC = 0.70). Nonthyroidal illness syndrome (fT3 < 2.0 pg/mL) was associated with a 7.05 OR of mortality (CI, 1.78-28.3, P = .005), and the product rT3 × fT3 ≤1.29 was associated with an 8.08 OR of mortality (CI, 3.14-24.2; P  < .0001).

The investigators acknowledged their analysis was limited to patients hospitalized with moderate-to-severe COVID-19 illness, and it was unclear whether a decrease in caloric intake, weight loss, or a combination of these factors led to decreased fT3 levels in people who were critically ill with COVID-19.

“Unexpectedly, NTIS was only observed in ∼6.5% patients,” stated the investigators. “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.”

In a related commentary (Moretti et al) researchers wrote, “Unique to this study was the novel observation that the fT3 × rT3 product showed the highest prognostic value of all parameters—including stereotypical inflammatory biomarkers—with a sensitivity and specificity of 80% and 57%, respectively.”

Disclosure: One of the main study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References

  1. Beltrão FEDL, Beltrão DCDA, Carvalhal G, et al. Thyroid hormone levels during hospital admission inform disease severity and mortality in COVID-19 patients. Thyroid. 2021;31(11):1639-1649. doi:10.1089/thy.2021.0225

2. Moretti B, Papaleontiou M. Prognostic value of thyroid hormone levels in hospitalized patients with moderate-to-severe COVID-19 infection. Clin Thyroidol. 2021;33(12):511-515. http://doi.org/10.1089/ct.2021;33.511-515