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

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

CONTEXT: 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. PURPOSE: To test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. METHODS: 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. 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 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. 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.