# Non-Thyroidal Illness Syndrome and Thyroid Autoimmunity in Hospitalized COVID-19 Patients: A Retrospective Study

## TL;DR

This study found that thyroid hormone changes and autoimmunity are common in hospitalized COVID-19 patients, especially those in the ICU, and may indicate disease severity.

## Contribution

The study introduces the clinical relevance of the fT3/rT3 ratio and combined autoantibody positivity in assessing severity of COVID-19.

## Key findings

- NTIS was more common in ICU patients (44.2%) compared to non-ICU patients (18.1%) and controls (1.8%).
- Thyroid autoantibodies were more prevalent in COVID-19 patients than in controls, with anti-TPO being the most common.
- The fT3/rT3 ratio was lowest in ICU patients, suggesting its potential as a severity marker.

## Abstract

Background: Thyroid dysfunction, including non-thyroidal illness syndrome (NTIS), is commonly observed in critically ill patients and has been reported in COVID-19, particularly in those with severe disease. NTIS is defined by low free triiodothyronine (fT3) with normal or low thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels. Thyroid autoantibodies may also reflect immune system activation. The relationship between thyroid hormone alterations, autoimmunity, and clinical severity in COVID-19 remains incompletely understood. Methods: We conducted a retrospective study of 276 patients hospitalized with COVID-19, including 138 in the intensive care unit (ICU) and 138 in general wards. A control group of 110 hospitalized, non-infected patients was also analyzed. Serum concentrations of TSH, fT3, fT4 and reverse T3 (rT3) were measured. The presence of anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and thyrotropin receptor antibodies (TRAb) was assessed. Results: NTIS was observed in 44.2% of ICU patients, 18.1% of non-ICU patients, and 1.8% of controls. The fT3/rT3 ratio was lowest in ICU patients (median 0.11 vs. 0.16 in non-ICU and 0.22 in controls). Thyroid autoantibodies were significantly more prevalent in COVID-19 patients than in controls, with anti-TPO antibodies being the most frequently detected. Their presence, even in patients without known thyroid disease, may reflect immune activation associated with SARS-CoV-2 infection. Conclusions: NTIS and thyroid autoimmunity are frequent in hospitalized COVID-19 patients and may reflect disease severity and immune activation. Our study highlights the prognostic relevance of routine thyroid testing, including the fT3/rT3 ratio and combined autoantibody positivity (notably the triple-positive pattern), by directly comparing ICU and non-ICU patients with a non-COVID control group.