The Association of TSH and Thyroid Hormones with Lymphopenia in Bacterial Sepsis and COVID-19

Context: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. Objective: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. Methods: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n=224) and COVID-19 patients (n=161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. Results: Only T3 significantly correlated (rho=0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n=56 per group). Severe lymphopenic COVID-19 patients (n=17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n=18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. Conclusion: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved.