Low free-T3 serum levels and prognosis of COVID-19: systematic review and meta-analysis

Clin Chem Lab Med. 2021 Aug 11;59(12):1906-1913. doi: 10.1515/cclm-2021-0805. Print 2021 Nov 25.


Objectives: There is increasing interest regarding the relationship between serum levels of free triiodothyronine (fT3) and outcomes of COronaVIrus Disease-19 (COVID-19) patients. As several recent reports have described a worse prognosis in patients with low fT3 levels, we performed a meta-analysis to assess the prognostic role of fT3 serum levels in patients with COVID-19 as this information could be clinically relevant for the management of these patients.

Methods: The methodology was registered in the International prospective register of systematic reviews (PROSPERO) database under the protocol number CRD42021260952. A systematic search was carried out on PubMed, Embase, Web of Science, and Scopus from May to June 2021 without time and language restrictions. The literature search strategy was based on the following keywords: (T3 OR fT3 OR triiodothyronine) AND (COVID-19) AND (prognosis OR survival).

Results: The literature search identified 163 studies. Seven retrospective studies met the inclusion and exclusion criteria and were included in the meta-analysis. The included studies had a total of 1,183 patients. From the analysis of the included studies, lower fT3 serum levels were consistently observed in intensive care unit (ICU) than in non-ICU patients and in non-survivors than survivors, respectively.

Conclusions: Serum fT3 concentrations are significantly lower in patients with severe COVID-19 than in non-severely ill patients and predict all-cause mortality of patients with severe COVID-19. Accordingly, fT3 may become a simple tool for stratified management of patients with severe COVID-19.

Keywords: COronaVIrus Disease-19 (COVID-19); cytokines; euthyroid sick syndrome; free triiodothyronine; intensive care unit.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • COVID-19 / mortality
  • COVID-19 / pathology*
  • COVID-19 / virology
  • Humans
  • Intensive Care Units
  • Odds Ratio
  • Prognosis
  • SARS-CoV-2 / isolation & purification
  • Survival Analysis
  • Triiodothyronine / blood*


  • Triiodothyronine