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

J Clin Endocrinol Metab. 2021 Jun 16;106(7):1994-2009. doi: 10.1210/clinem/dgab148.


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 (ρ = 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.

Keywords: COVID-19; inflammation; lymphocyte; metabolism; sepsis; thyroid.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19 / blood
  • COVID-19 / complications*
  • COVID-19 / immunology
  • Euthyroid Sick Syndromes / blood
  • Euthyroid Sick Syndromes / diagnosis*
  • Euthyroid Sick Syndromes / immunology
  • Female
  • Greece
  • Humans
  • Lymphocyte Count
  • Lymphopenia / blood
  • Lymphopenia / diagnosis
  • Lymphopenia / immunology*
  • Male
  • Netherlands
  • Retrospective Studies
  • SARS-CoV-2 / immunology
  • Sepsis / blood
  • Sepsis / complications*
  • Sepsis / immunology
  • Thyroid Hormones / blood
  • Thyroid Hormones / immunology
  • Thyrotropin / blood
  • Thyrotropin / immunology


  • Thyroid Hormones
  • Thyrotropin