Abnormal Thyroid Function Is Associated 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, Johannes W A; Van Herwaarden, Antonius E; Jaeger, Martin; Netea, Mihai G; Giamarellos-Bourboulis, Evangelos J; Netea-Maier, Romana T

Background: Lymphopenia is a key feature of immune dysfunction in bacterial sepsis and COVID-19 patients and is associated with poor clinical outcomes, but the cause is largely unknown. These severely ill patients may also present with thyroid function abnormalities, so-called non-thyroidal illness syndrome (NTIS), and several studies have suggested that TSH, thyroxin (T4) and triiodothyronine (T3) play a crucial role in the homeostatic regulation and function of lymphocyte populations. Aim: The purpose of this study was to test the hypothesis that abnormal thyroid function correlates with lymphopenia in severly ill patients with bacterial sepsis or COVID-19. Methods: Retrospective analysis of absolute lymphocyte counts and circulating TSH, T4, FT4, T3, albumin and inflammatory biomarkers was performed in two independent cohorts of bacterial sepsis (n=224) and hospitalized COVID-19 patients (n=35). Results: Only T3 correlated (rho=0.252, p-value: <0.001) with lymphocyte counts in the bacterial sepsis population and lower concentrations were found in severe lymphopenic compared to non-lympopenic patients (p-value: <0.001; n=56 per group). Severe lymphopenic COVID-19 patients (n=17) showed significantly lower plasma concentrations of TSH, T4, FT4 and T3 (p-value: 0.026, <0.001, 0.001, <0.001, respectively) compared to patients withouth lymphopenia (n=18), and demonstrated significantly increased values of the inflammatory parameters IL-6, C-reactive protein and ferritin (p-value: <0.001, 0.023, and 0.008, respectively). Remarkable, after one week follow-up, the majority of (12/15) COVID-19 patients showed quantitative recovery of their lymphocyte numbers, while TSH and thyroid hormones remained mainly disturbed. Conclusions: Abnormal thyroid function correlates with low lymphocyte counts in severe sepsis and COVID-19 patients, but future studies need to establish whether a causal relationship is involved.