Renin-Angiotensin System overactivation in polycystic ovary syndrome, a risk for SARS-CoV-2 infection?

Abstract

Background The SARS-CoV-2 coronavirus gains entry to target cells via the angiotensin-converting enzyme 2 (ACE2) receptor present on cells in blood vessels, lungs, heart, intestines, and kidneys. Renin-Angiotensin System (RAS) overactivity has also been described in metabolic syndrome, type 2 diabetes (T2D) and obesity, conditions shared by women with polycystic ovary syndrome (PCOS) We hypothesized that RAS overactivity may be present in PCOS. Methods We determined plasma levels of RAS-related proteins in a cohort of age matched control women (n = 97) and women with PCOS (n = 146). Plasma levels of RAS-related proteins (ACE2, Renin and Angiotensinogen (AGT)) were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Results PCOS women had a higher BMI (p < 0.001), systolic (p < 0.0001) and diastolic (p < 0.05) blood pressure, waist circumference (p < 0.0001), testosterone (p < 0.0001), free androgen index (p < 0.0001) and CRP (p < 0.0001). Renin was elevated in PCOS (p < 0.05) and angiotensinogen was lower in PCOS (p < 0.05), indicating overactivity of the RAS system in PCOS. ACE2 levels were lower in PCOS (p < 0.05), suggesting that PCOS women are at risk for development of hypertension. Conclusion RAS proteins levels differed between PCOS and control women, suggesting that the insulin resistance inherent in PCOS may predispose these women to more severe COVID-19 infection.

COVID-19 biomarkers for severity mapped to polycystic ovary syndrome

“…These protein panels target biological processes involved in vessel damage, platelet degranulation, the coagulation cascade and the acute phase response [ 1 ], with greater protein changes dependent on the COVID-19 severity. However, it is observed that in metabolic conditions such as polycystic ovary syndrome expressed proteins differ compared to control women [ 2 ] and PCOS patients have increased platelet aggregation and decreased plasma fibrinolytic activity, resulting in a prothrombotic propensity [ 3 , 4 ], with elevated coagulation markers [ 5 ]. Therefore, any biomarkers reflecting COVID-19 disease and its severity would necessarily have to be independent of differentially-expressed proteins relating to other conditions; therefore, this proteomic analysis was undertaken in women with and without PCOS to compare with the proteomic biomarkers recently described in COVID-19 using shotgun proteomics followed by parallel reaction monitoring [ 1 ].…”

“…146 PCOS and 97 control women who presented sequentially to the Department of Endocrinology, Hull and East Yorkshire Hospitals NHS Trust were recruited to the local PCOS biobank (ISRCTN70196169) [ 2 ]. PCOS diagnosis was based on all three Rotterdam consensus diagnostic criteria.…”

The relationship of soluble neuropilin-1 to severe COVID-19 risk factors in polycystic ovary syndrome

“…As reported previously [ 10 ], cohorts were age-matched, but PCOS women had increased insulin resistance, androgens and CRP (p < 0.001); systolic and diastolic blood pressure, and waist circumference were higher (p < 0.05). As reported, RAS system overactivity was found with elevated renin, and decreased angiotensinogen and ACE2 in PCOS (p < 0.05), indicative of increased hypertensive risk [ 10 ].…”

“…Polycystic ovary syndrome (PCOS), a cardiometabolic disease encompassing metabolic syndrome, insulin resistance [ 7 ] and obesity with increased T2D risk [ 8 ], also predisposes to severe COVID-19 disease, as suggested by case reports of PCOS women infected by SARS-CoV-2 [ 9 ]. We have reported higher renin and lower angiotensinogen levels, indicating RAS hyperactivation, in PCOS [ 10 ]. Since RAS-related proteins, NRP1 and VEGF, are implicated in COVID-19 severity, we hypothesized that increased risk of severe COVID-19 in PCOS may be reflected in altered soluble NRP1 (sNRP1) levels and their association with RAS-related proteins and VEGF.…”

“…“146 PCOS and 97 control women who presented sequentially to the Department of Endocrinology, Hull and East Yorkshire Hospitals NHS Trust were recruited to the local PCOS biobank (ISRCTN70196169)” [ 10 ]. “PCOS diagnosis was based on all three Rotterdam consensus diagnostic criteria, these specifically being hyperandrogenism, either clinical or biochemical with a Ferriman-Gallwey score of >8 and free androgen index >4.5, oligomenorrhea (defined as ≤9 menses/year) or amenorrhea (defined as lack of menses for ≥3-months) and polycystic ovaries (≥12 antral follicles in ≥1 ovary or ovarian volume of ≥10cm 3 ) as determined by transvaginal ultrasonography [ 11 ].…”