The association of TSH and thyroid hormones with lymphopenia in bacterial sepsis and COVID-19.

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Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and COVID-19 and associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called non-thyroidal illness syndrome (NTIS), and several studies have linked TSH and the thyroid hormones thyroxine (T4) and triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations.To test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections.Retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin and inflammatory biomarkers was performed in two 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.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 non-lympopenic 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 one week follow-up, the majority (12/15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, while TSH and thyroid hormones remained mainly disturbed.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.



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Authors: Inge Grondman, Aline H de Nooijer, Nikolaos Antonakos, Nico A F Janssen, Maria Mouktaroudi, Konstantinos Leventogiannis, Marco Medici, Jan W A Smit, Antonius E van Herwaarden, Leo A B Joosten, Frank L van der Veerdonk, Peter Pickkers, Matthijs Kox, Martin Jaeger, Mihai G Netea, Evangelos J Giamarellos-Bourboulis, Romana T Netea-Maier

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