Activation of Type I and Type II Interferon signaling in SARS-CoV-2-positive thyroid tissue of patients dying from COVID-19

Poma, Anello Marcello; Basolo, Alessio; Bonuccelli, Diana; Proietti, Agnese; Macerola, Elisabetta; Ugolini, Clara; Torregrossa, Liborio; Alì, Greta; Giannini, Riccardo; Vignali, Paola; Santini, Ferruccio; Toniolo, Antonio; Basolo, Fulvio

BACKGROUND: Thyroid dysfunctions have been reported after 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 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. RT-PCR 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 nine out 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 up-regulation 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.