Abstract
BackgroundWomen with polycystic ovary syndrome (PCOS) often have vitamin D deficiency, a known risk factor for severe COVID-19 disease. Alveolar macrophage-derived cytokines contribute to the inflammation underlying pulmonary disease in COVID-19. We sought to determine if basal macrophage activation, as a risk factor for COVID-19 infection, was present in PCOS and, if so, was further enhanced by vitamin D deficiency.MethodsA cross-sectional study in 99 PCOS and 68 control women who presented sequentially. Plasma levels of a macrophage-derived cytokine panel were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement. Vitamin D was measured by tandem mass spectroscopy.ResultsVitamin D was lower in PCOS women (p<0.0001) and correlated negatively with body mass index (BMI) in PCOS (r=0.28, p=0.0046). Basal macrophage activation markers CXCL5, CD163 and MMP9 were elevated, whilst protective CD200 was decreased (p<0.05); changes in these variables were related to, and fully accounted for, by BMI. PCOS and control women were then stratified according to vitamin D concentration. Vitamin D deficiency was associated with decreased CD80 and IFN-γ in PCOS and IL-12 in both groups (p<0.05). These factors, important in initiating and maintaining the immune response, were again accounted for by BMI.ConclusionBasal macrophage activation was higher in PCOS with macrophage changes related with increased infection risk associating with vitamin D; all changes were BMI dependent, suggesting that obese PCOS with vitamin D deficiency may be at greater risk of more severe COVID-19 infection, but that it is obesity-related rather than an independent PCOS factor.
Highlights
Women with polycystic ovary syndrome (PCOS) often have vitamin D deficiency, a known risk factor for severe COVID-19 disease
Inflammation has been suggested to underlie insulin resistance and obesity in PCOS caused by macrophage stimulation [11]; we hypothesized that there would be an increase in activated macrophages in those subjects with PCOS that would be further increased by vitamin D deficiency, predisposing these women to increased risk for severe COVID-19 disease
Basal macrophage activation markers chemokine ligand 5 (CXCL5), Cluster of Differentiation 163 (CD163) and Matrix metalloproteinase-9 (MMP9) were elevated, whilst the protective Cluster of Differentiation 200 (CD200) was decreased (p
Summary
Women with polycystic ovary syndrome (PCOS) often have vitamin D deficiency, a known risk factor for severe COVID-19 disease. It has been suggested that these features of PCOS put subjects at a higher risk for severe COVID-19 infection [2, 3]. In severe COVID-19 disease, acute respiratory distress syndrome (ARDS) results, caused by an unconstrained systemic inflammation to which differing populations of macrophages (resident alveolar macrophages (AMs), and recruited macrophages from the circulation) contribute [8]. Inflammation has been suggested to underlie insulin resistance and obesity in PCOS caused by macrophage stimulation [11]; we hypothesized that there would be an increase in activated macrophages in those subjects with PCOS that would be further increased by vitamin D deficiency, predisposing these women to increased risk for severe COVID-19 disease
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