Adrenal tropism of SARS-CoV-2 and adrenal findings in a post-mortem case series of patients with severe fatal COVID-19

Paul, Tanja; Ledderose, Stephan; Bartsch, Harald; Sun, Na; Soliman, Sarah; Märkl, Bruno; Ruf, Viktoria; Herms, Jochen; Stern, Marcel; Keppler, Oliver T.; Delbridge, Claire; Müller, Susanna; Piontek, Guido; Kimoto, Yuki Schneider; Schreiber, Franziska; Williams, Tracy Ann; Neumann, Jens; Knösel, Thomas; Schulz, Heiko; Spallek, Ria; Graw, Matthias; Kirchner, Thomas; Walch, Axel; Rudelius, Martina

doi:10.1038/s41467-022-29145-3

Cited by 27 publications

(37 citation statements)

References 48 publications

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“…Susceptible cells also need to express co-receptors required for virus internalization, such as transmembrane protease serine 2 or furins. Several reports, including our own, have confirmed the expression of these receptors in the adrenal gland 3 , 4 . Moreover, these reports provided evidence that SARS-CoV-2 might not only target human adrenocortical cells 3 , 4 , but might also actively replicate in these cells 4 .…”

Section: Is Sars-cov-2 Targeting Adrenal Cells?supporting

confidence: 71%

“…Several reports, including our own, have confirmed the expression of these receptors in the adrenal gland 3 , 4 . Moreover, these reports provided evidence that SARS-CoV-2 might not only target human adrenocortical cells 3 , 4 , but might also actively replicate in these cells 4 . For example, SARS-CoV-2 RNA and protein were detected in 45% of adrenal glands obtained from patients who died due to a critical course of COVID-19 infection 3 .…”

Section: Is Sars-cov-2 Targeting Adrenal Cells?supporting

confidence: 71%

“…For example, SARS-CoV-2 RNA and protein were detected in 45% of adrenal glands obtained from patients who died due to a critical course of COVID-19 infection 3 . Interestingly, SARS-CoV-2 was also detected in adrenal endothelial cells 4 . However, no proof of an active replication could be found, indicating that SARS-CoV-2 is passively transmitted through the adrenal vascular system 4 .…”

Section: Is Sars-cov-2 Targeting Adrenal Cells?mentioning

confidence: 99%

“…Interestingly, SARS-CoV-2 was also detected in adrenal endothelial cells 4 . However, no proof of an active replication could be found, indicating that SARS-CoV-2 is passively transmitted through the adrenal vascular system 4 . In addition, SARS-CoV-2 infection was associated with increased inflammation and activation of programmed cell death pathways in human adrenocortical cells 3 , 4 .…”

Section: Is Sars-cov-2 Targeting Adrenal Cells?mentioning

confidence: 99%

“…Although cellular damage due to SARS-CoV-2 infections might not lead to adrenal insufficiency, COVID-19 associated haemorrhages and infarctions might. Interestingly, histopathological studies analysing tissues obtained from autopsies of patients with COVID-19 found fibrin and microthrombi deposition in adrenal capillaries 4 . The ample vascularization and blood flow in the adrenals illustrate the susceptibility of the adrenal glands to vascular damage.…”

Section: Covid-19 and Adrenal Insufficiencymentioning

confidence: 99%

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Is there a role for the adrenal glands in long COVID?

2022

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Section: Is Sars-cov-2 Targeting Adrenal Cells?supporting

confidence: 71%

Section: Is Sars-cov-2 Targeting Adrenal Cells?supporting

confidence: 71%

Section: Is Sars-cov-2 Targeting Adrenal Cells?mentioning

confidence: 99%

Section: Is Sars-cov-2 Targeting Adrenal Cells?mentioning

confidence: 99%

Section: Covid-19 and Adrenal Insufficiencymentioning

confidence: 99%

See 3 more Smart Citations

Is there a role for the adrenal glands in long COVID?

2022

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

et al. 2023

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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 • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.

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COVID-19 pandemic and adrenals: deep insights and implications in patients with glucocorticoid disorders

et al. 2023

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Purpose Coronavirus disease-19 (COVID-19) has spread throughout the world. It was initially defined as a potentially severe syndrome affecting the respiratory tract, but it has since been shown to be a systemic disease with relevant extrapulmonary manifestations that increase mortality. The endocrine system has been found to be vulnerable to COVID-19 infection. The current review aims to evaluate the available data on the impact of COVID-19 infection and treatment, as well as COVID-19 vaccines, on adrenal gland function, particularly in patients with GC disorders. Methods A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. Results Adrenal viral tropism and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the adrenal glands have been demonstrated, and adrenal insufficiency (AI) is a rare, but potentially severe complication in COVID-19 disease, whose recognition can be difficult if only for the empirical treatments administered in the early stages. Glucocorticoid (GC) treatment have had a pivotal role in preventing clinical deterioration in patients with COVID-19, but long-term GC use may increase COVID-19-related mortality and the development of iatrogenic AI. Patients with GC disorders, especially AI and Cushing’s syndrome, have been identified as being at high risk of COVID-19 infection and complications. Published evidence suggests that AI patient awareness and proper education may help adjust GC replacement therapy appropriately when necessary, thereby reducing COVID-19 severity. The COVID-19 pandemic has had an impact on AI management, particularly in terms of adherence to patients’ care plans and self-perceived challenges. On the other hand, published evidence suggests that the clinical course of COVID-19 may be affected by the severity of hypercortisolism in patients with CS. Therefore, to ameliorate the risk profile in these patients, cortisol levels should be adequately controlled, along with careful monitoring of metabolic and cardiovascular comorbidities. To date, the COVID-19 vaccine remains the only available tool to face SARS-CoV-2, and it should not be treated differently in patients with AI and CS. Conclusion SARS-CoV-2 infection has been linked to adrenal damage and AI is a rare complication in COVID-19 disease, requiring prompt recognition. Educational efforts and patient awareness may reduce COVID-19 severity in patients with AI. Control of cortisol levels and monitoring of complications may improve the clinical course of COVID-19 in patients with CS.

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Adrenal tropism of SARS-CoV-2 and adrenal findings in a post-mortem case series of patients with severe fatal COVID-19

Cited by 27 publications

References 48 publications

Is there a role for the adrenal glands in long COVID?

Is there a role for the adrenal glands in long COVID?

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

COVID-19 pandemic and adrenals: deep insights and implications in patients with glucocorticoid disorders

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