Activation of Type I and Type II Interferon Signaling in SARS-CoV-2-Positive Thyroid Tissue of Patients Dying from COVID-19

Thyroid. 2021 Dec;31(12):1766-1775. doi: 10.1089/thy.2021.0345.


Background: Thyroid dysfunctions have been reported after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, the biological mechanisms behind these conditions remain unexplored. Herein, we report on changes of the immune transcriptome in autoptic thyroid tissues of people who have died from coronavirus disease 2019 (COVID-19). Methods: Twenty-five autoptic thyroid specimens of subjects dying from COVID-19 were investigated. Eleven autoptic thyroid specimens of subjects dying from causes other than infectious conditions served as controls. RNA transcripts of 770 immune-related genes together with RNA genomes of multiple coronavirus types were measured by the nCounter system. Reverse transcription-polymerase chain reaction for two SARS-CoV-2 genes was used to assess virus positivity. Results were validated by immunohistochemistry. Results: The SARS-CoV-2 genome and antigens were detected in 9 of 25 (36%) thyroid specimens from the COVID-19 cohort. Virus-negative thyroid tissues from COVID-19 subject did not show changes of gene transcription nor significant numbers of infiltrating immune cells. Conversely, SARS-CoV-2-positive thyroid specimens showed marked upregulation of immune genes, especially those proper of the type I and type II interferon (IFN) pathways. In infected tissues, infiltrates of innate immune cells (macrophages and polymorphonuclear neutrophils) were prevalent. Conclusions: The thyroid gland can be directly infected by the SARS-CoV-2. Infection strongly activates IFN pathways. The direct viral insult combined with an intense immune response may trigger or worsen thyroid conditions in predisposed individuals.

Keywords: COVID-19; SARS-CoV-2; autopsy; interferons; thyroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Autopsy
  • COVID-19 / metabolism*
  • COVID-19 / mortality
  • Cohort Studies
  • Death
  • Female
  • Genome, Viral
  • Humans
  • Immunity, Innate
  • Interferon Type I / metabolism*
  • Interferon-gamma / metabolism*
  • Macrophages / cytology
  • Male
  • Middle Aged
  • Neutrophils / cytology
  • RNA, Messenger / metabolism
  • SARS-CoV-2*
  • Signal Transduction
  • Thyroid Gland / immunology
  • Thyroid Gland / metabolism*
  • Thyroid Gland / virology*


  • Interferon Type I
  • RNA, Messenger
  • Interferon-gamma