Analysis of 2019-nCoV receptor ACE2 expression in different tissues and its significance study

Han, Tao; Kang, Jian; Gao, Li; Ge, Jing; Gu, Jia

doi:10.21037/atm-20-4281

Cited by 67 publications

(72 citation statements)

References 21 publications

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“…Evidence suggests that sex steroids can influence ACE2 expression in the respiratory tract, and that higher ACE2 levels may be causally related to increased COVID-19 severity [67][68][69][70][71]. However, studies investigating ACE2 expression in respiratory tract tissues by sex have not consistently shown higher expression in males, highlighting that levels of ACE2 may not fully explain the observed male bias in severe COVID-19 disease [55,[71][72][73][74]. While our data and several other studies demonstrate robust expression of ACE2 in the human placenta that may vary by gestational age [12,15,[17][18][19]75,76], few studies have evaluated sex-specific placental ACE2 expression, and these have reported conflicting results [78,79].…”

Section: Discussionmentioning

confidence: 99%

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

Shook

Bordt

Meinsohn

et al. 2021

Preprint

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Background: Sex differences in vulnerability to and severity of SARS-CoV-2 infection have been described in non-pregnant populations. ACE2 and TMPRSS2, host molecules required for viral entry, are regulated by sex steroids and expressed in the placenta. We sought to investigate whether placental ACE2 and TMPRSS2 expression vary by fetal sex and in the presence of maternal SARS-CoV-2 infection. Methods: Placental ACE2 and TMPRSS2 were quantified in 68 pregnant individuals (38 SARS-CoV-2 positive, 30 SARS-CoV-2 negative) delivering at Mass General Brigham from April to June 2020. Maternal SARS-CoV-2 status was determined by nasopharyngeal RT-PCR. Placental SARS-CoV-2 viral load was quantified. RTqPCR was performed to quantify expression of ACE2 and TMPRSS2 relative to the reference gene YWHAZ. Western blots were performed on placental homogenates to quantify protein levels. The impact of fetal sex and SARS-CoV-2 exposure on ACE2 and TMPRSS2 expression was analyzed by 2-way ANOVA. Results: SARS-CoV-2 virus was undetectable in all placentas. Maternal SARS-CoV-2 infection impacted TMPRSS2 placental gene and protein expression in a sexually dimorphic fashion (2-way ANOVA interaction p-value: 0.002). We observed no impact of fetal sex or maternal SARS-CoV-2 status on placental ACE2 gene or protein expression. Placental TMPRSS2 expression was significantly correlated with ACE2 expression in males (Spearman's rho=0.54, p=0.02) but not females (rho=0.23, p=0.34) exposed to maternal SARS-CoV-2. Conclusions: Sex differences in placental TMPRSS2 but not ACE2 were observed in the setting of maternal SARS-CoV-2 infection. These findings may have implications for offspring vulnerability to placental infection and vertical transmission.These findings may have implications for offspring vulnerability to placental infection and vertical transmission.

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Section: Discussionmentioning

confidence: 99%

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

Shook

Bordt

Meinsohn

et al. 2021

Preprint

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“…ACE2 mRNA expression was reported also in hypothalamus and pituitary gland cells [ 50 ]. Moreover, in a previous study, SARS-CoV was detected in pituitary tissues from patients who died from SARS [ 51 ].…”

Section: Main Pituitary Manifestations Of Covid-19mentioning

confidence: 99%

COVID-19 and the pituitary

et al. 2021

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Background Despite COVID-19 being identified as severe respiratory viral infection, progressively many relevant endocrine manifestations have been reported greatly contributing to the severity of the clinical presentation. Systemic involvement in COVID-19 is due to the ubiquitous expression of angiotensin-converting enzyme 2 (ACE2) receptor, responsible for the entry in the cells of SARS-CoV-2, Several reports in humans and animal models showed a significant ACE2 mRNA expression in hypothalamus and pituitary cells. Moreover, higher mortality and poorer outcomes have been widely described in COVID-19 patients with obesity, diabetes and vertebral fractures, which are all highly prevalent in subjects with pituitary dysfunctions. Aim To review the main endocrine manifestations of COVID-19 with their possible implications for pituitary diseases, the possible direct and indirect involvement of the pituitary gland in COVID-19, the impact of COVID-19 on the management of established pituitary diseases which can be already at increased risk for worse outcomes and on neurosurgical activities as well as vaccination. Conclusions Our review underlines that there could be a specific involvement of the pituitary gland which fits into a progressively shaping endocrine phenotype of COVID-19. Moreover, the care for pituitary diseases need to continue despite the restrictions due to the emergency. Several pituitary diseases, such as hypopituitarism and Cushing disease, or due to frequent comorbidities such as diabetes may be a risk factor for severe COVID-19 in affected patients. There is the urgent need to collect in international multicentric efforts data on all these aspects of the pituitary involvement in the pandemic in order to issue evidence driven recommendations for the management of pituitary patients in the persistent COVID-19 emergency.

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“…These receptors are expressed on a broad range of tissue. The highest levels of ACE2 expression and activity were found at the small intestine, kidney, heart, salivary glands, testicles, and thyroid, whereas lower levels were observed in the brain, skin, pituitary, and skeletal muscles [17,18]. Thyroid follicular cells express ACE2 as suggested by direct molecular analysis of surgical samples of thyroid tissue [19], leading the gland to be susceptible to SARS-CoV-2 injury once the infection has occurred.…”

Section: Biochemical and Immunological Relationship Between Sars-cov-2 And Thyroid Glandmentioning

confidence: 99%

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects

Lisco

Tullio

Jirillo

et al. 2021

J Endocrinol Invest

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Background Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. Objective and methods To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: “sars cov 2”, “covid 19”, “subacute thyroiditis”, “atypical thyroiditis”, “chronic thyroiditis”, “hashimoto’s thyroiditis”, “graves’ disease”, “thyroid nodule”, “differentiated thyroid cancer”, “medullary thyroid cancer”, “methimazole”, “levothyroxine”, “multikinase inhibitor”, “remdesivir”, “tocilizumab”. Data were collected, analyzed, and discussed to answer the following clinical questions: “What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?”; “Could medical management of thyroid diseases influence the clinical course of COVID-19?”; “Does medical management of COVID-19 interfere with thyroid function?”; “Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?”. Results SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. Discussion Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.

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Analysis of 2019-nCoV receptor ACE2 expression in different tissues and its significance study

Cited by 67 publications

References 21 publications

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

Placental expression of ACE2 and TMPRSS2 in maternal SARS-CoV-2 infection: are placental defenses mediated by fetal sex?

COVID-19 and the pituitary

Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects

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