Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19

Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes.Key messages center dot SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid.center dot Infection of endocrine organs induces interferon response.center dot Interferon response is observed in adipose tissue independently of virus presence.center dot Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19.center dot Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.

Automated summary

Altered gene expression in endocrine organs is observed in COVID-19, with enhanced interferon response and specific changes in endocrine-specific genes. Adipose tissue shows independent enhanced interferon response regardless of virus presence. Important genes such as insulin, thyroid-stimulating hormone receptor, and leptin are affected in COVID-19.