BACKGROUND
Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 virus infection. It was first detected in December 2019 and has become the fifth documented pandemic since the 1918 flu pandemic. It has led to more than 248 million cases and 5 million deaths worldwide. COVID-19 mostly effects the respiratory system, but many patients also develop changes in thyroid function tests. These changes are like the changes that occur in any life-threatening illness and known as non-thyroidal illness syndrome (NTIS). Serum triiodothyronine (FT3), serum thyroxine (FT4) levels decrease and reverse triiodothyronine (rT3) levels increase. There have been reports showing an association with low FT3 levels with COVID-19 severity, 28-day death rate, and hospitalization expenses in the intensive care unit. However, there were weaknesses in the previous studies, such as small number of patients, design of the study, and inconsistent collection of thyroid function tests.

We need to understand the factors that may help us recognize which patients may develop more severe illness to treat them successfully. Currently we use several proinflammatory markers for this purpose. These are molecules made by immune system that can promote inflammation. This study was designed to evaluate thyroid hormone levels and presence of NTIS in patients admitted with COVID-19 and to investigate whether thyroid hormone levels were associated with pro-inflammatory markers and COVID-19 severity and death rate.

THE FULL ARTICLE TITLE
Beltrão FEL et al 2021 Thyroid hormone levels during hospital admission inform disease severity and mortality in COVID-19 patients. Thyroid. Epub 2021 Sep 9. PMID: 34314259.

SUMMARY OF THE STUDY
The researchers studied 245 patients who were admitted with COVID-19 to a referral hospital (Metropolitan Hospital Dom Jose Maria Pires) in Brazil from June to August 2020. SARS-Cov-2 infection was confirmed in all patients by PCR testing. NTIS was defined as serum FT3 levels <2 pg/ml, FT4 and TSH levels within or below the normal reference ranges.

All patients had a chest CT (computed tomography) scan when they were admitted. Researchers calculated severity scores based on the extent of disease in the lungs. Noncritical infection was defined as breathing <30 breaths per minute, oxygen saturation <93% at rest, > 50% lung injury as estimated by CT scan. Critical infection was defined as respiratory failure requiring a machine to help with breathing (mechanical ventilation), sudden drop in blood flow and pressure (shock), or organ failure requiring treatment in intensive care unit (ICU). Blood samples were collected within 48 hours of admission and prior to any treatment that may affect thyroid hormone or inflammatory marker levels.

The average age was 62 years (range, 49-74.5) and 145 (59.1%) were men. The average hospital stay was 8.3 days. A total of 58 (23.6%) patients were admitted to the ICU and 41 (16.7%) of these patients later died. Only 54 (22%) patients had normal thyroid hormone levels while 154 (62.8%) had elevated rT3 levels and 18 had only high serum fT4 levels. Only 6.5% of patients had NTIS. Critically ill patients had lower serum fT3 and high normal rT3 levels while rT3 levels were higher in noncritical patients. Serum fT3, rT3, and the product of fT3 x rT3 showed strong association with COVID-19 severity and death rate. Overall, 8 of the 11 inflammation markers (IL-6, D-dimer, lactate dehydrogenase, albumin, CRP, neutrophils, neutrophil/ lymphocyte ratio, and hemoglobin) predicted disease severity and death rate. The strongest predictors of death rate and length of stay were fT3 x rT3, neutrophil/lymphocyte ratio, CRP, neutrophil count and serum fT3.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
The findings from this study are important for several reasons. This was one of the largest studies that reported thyroid tests of patients hospitalized with COVID-19. Serum fT3, rT3 and the product of fT3 x rT3 were able to help recognize which patients were likely to have more severe disease or die from it. It is the first study that investigated whether the product of rT3 x fT3 would show an association with disease severity. This marker was better as a predictor than the currently used methods.

These are promising findings that can help the management of patients hospitalized for COVID-19 but need to be confirmed with other large, carefully designed studies.

— Ebru Sulanc, MD

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