{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:52:47Z","timestamp":1792687967308,"version":"4.5.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Women 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vitamin D was lower in PCOS women (p&amp;lt;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&amp;lt;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-\u03b3 in PCOS and IL-12 in both groups (p&amp;lt;0.05). These factors, important in initiating and maintaining the immune response, were again accounted for by BMI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Basal 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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.638621","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T09:16:21Z","timestamp":1614244581000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Vitamin D Association With Macrophage-Derived Cytokines in Polycystic Ovary Syndrome: An Enhanced Risk of COVID-19 Infection?"],"prefix":"10.3389","volume":"12","author":[{"given":"Abu Saleh Md","family":"Moin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thozhukat","family":"Sathyapalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Atkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-1549","article-title":"Glucose intolerance in polycystic ovary syndrome\u2013a position statement of the Androgen Excess Society","volume":"92","author":"Salley","year":"2007","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metop.2020.100052","article-title":"Renin-Angiotensin System Overactivation in Polycystic Ovary Syndrome, a Risk for SARS-CoV-2 Infection","volume":"7","author":"Moin","year":"2020","journal-title":"Metab Open"},{"key":"B3","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1186\/s12916-020-01697-5","article-title":"Polycystic ovary syndrome (PCOS) and COVID-19: an overlooked female patient population at potentially higher risk during the COVID-19 pandemic","volume":"18","author":"Kyrou","year":"2020","journal-title":"BMC Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00013","article-title":"Association of Vitamin D Metabolites With Embryo Development and Fertilization in Women With and Without PCOS Undergoing Subfertility Treatment","volume":"10","author":"Cunningham","year":"2019","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-020-01570-8","article-title":"The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality","volume":"32","author":"Ilie","year":"2020","journal-title":"Aging Clin Exp Res"},{"key":"B6","first-page":"81","article-title":"Vitamin D and Inflammation: Potential Implications for Severity of Covid-19","volume":"113","author":"Laird","year":"2020","journal-title":"Ir Med J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2020.04.050","article-title":"Vitamin D concentrations and COVID-19 infection in UK Biobank","volume":"14","author":"Hastie","year":"2020","journal-title":"Diabetes Metab Syndr"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201107-1343ED","article-title":"The lung macrophage: a Jack of all trades","volume":"184","author":"Misharin","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59643","article-title":"Macrophage plasticity and polarization: in vivo veritas","volume":"122","author":"Sica","year":"2012","journal-title":"J\u00a0Clin Invest"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.2741\/2692","article-title":"Macrophage activation and polarization","volume":"13","author":"Martinez","year":"2008","journal-title":"Front Biosci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2011.12.003","article-title":"Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction","volume":"77","author":"Gonz\u00e1lez","year":"2012","journal-title":"Steroids"},{"key":"B12","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.fertnstert.2003.10.004","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome","volume":"81","year":"2004","journal-title":"Fertil Steril"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/cen.13517","article-title":"Anti-Mullerian hormone measurement for the diagnosis of polycystic ovary syndrome","volume":"88","author":"Sathyapalan","year":"2018","journal-title":"Clin Endocrinolo"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3795","DOI":"10.1038\/s41598-018-22176-1","article-title":"Salivary and serum androgens with anti-Mullerian hormone measurement for the diagnosis of polycystic ovary syndrome","volume":"8","author":"Sathyapalan","year":"2018","journal-title":"Sci Rep"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/nu11010188","article-title":"A Randomized, Controlled Trial of Vitamin D Supplementation on Cardiovascular Risk Factors, Hormones, and Liver Markers in Women with Polycystic Ovary Syndrome","volume":"11","author":"Javed","year":"2019","journal-title":"Nutrients"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J Clin Endocrinol Metab"},{"key":"B17","doi-asserted-by":"publisher","first-page":"4750","DOI":"10.1038\/s41598-020-66189-1","article-title":"Effect of induced hypoglycemia on inflammation and oxidative stress in type 2 diabetes and control subjects","volume":"10","author":"Kahal","year":"2020","journal-title":"Sci Rep"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-1115","article-title":"Renin-Angiotensin System Overactivation in Type 2 Diabetes: A Risk for SARS-CoV-2 Infection","volume":"43","author":"Moin","year":"2020","journal-title":"Diabetes Care"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026332","article-title":"From SOMAmer-based biomarker discovery to diagnostic and clinical applications: a SOMAmer-based, streamlined multiplex proteomic assay","volume":"6","author":"Kraemer","year":"2011","journal-title":"PloS One"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15345","article-title":"Connecting genetic risk to disease end points through the human blood plasma proteome","volume":"8","author":"Suhre","year":"2017","journal-title":"Nat Commun"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30434-5","article-title":"Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study","volume":"20","author":"Carsana","year":"2020","journal-title":"Lancet Infect Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0331-4","article-title":"Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages","volume":"20","author":"Merad","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.29252\/ijrm.15.10.4","article-title":"CXC Ligand 5 cytokine serum level in women with polycystic ovary syndrome and normal body mass index: A case-control study","volume":"15","author":"Zohrabi","year":"2017","journal-title":"Int J Reprod Biomed"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/00365513.2011.626868","article-title":"Soluble CD163","volume":"72","author":"M\u00f8ller","year":"2012","journal-title":"Scand J Clin Lab Invest"},{"key":"B25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1055\/s-0042-101028","article-title":"A Study of Serum Soluble CD 163 Levels in Women with Polycystic Ovary Syndrome","volume":"48","author":"Oru\u00e7","year":"2016","journal-title":"Horm Metab Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/der096","article-title":"No difference in markers of adipose tissue inflammation between overweight women with polycystic ovary syndrome and weight-matched controls","volume":"26","author":"Lindholm","year":"2011","journal-title":"Hum Reprod"},{"key":"B27","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1530\/REP-15-0340","article-title":"Matrix metalloproteinases 2 and 9 and MMP9\/NGAL complex activity in women with PCOS","volume":"151","author":"Ranjbaran","year":"2016","journal-title":"Reproduction"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13492","article-title":"CD200 increases alternatively activated macrophages through cAMP-response element binding protein - C\/EBP-beta signaling","volume":"136","author":"Hayakawa","year":"2016","journal-title":"J Neurochem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20225811","article-title":"Correlation of Vitamin D with Inflammatory Cytokines, Atherosclerotic Parameters, and Lifestyle Factors in the Setting of Heart Failure: A 12-Month Follow-Up Study","volume":"20","author":"Roffe-Vazquez","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B30","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1111\/j.1365-2567.2009.03155.x","article-title":"Efficiency of T-cell costimulation by CD80 and CD86 cross-linking correlates with calcium entry","volume":"129","author":"Thiel","year":"2010","journal-title":"Immunology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142735","article-title":"Interleukin-12 (IL-12)\/STAT4 Axis Is an Important Element for \u03b2-Cell Dysfunction Induced by Inflammatory Cytokines","volume":"10","author":"Weaver","year":"2015","journal-title":"PloS One"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1039\/C6PP00355A","article-title":"The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease","volume":"16","author":"Abhimanyu","year":"2017","journal-title":"Photochem Photobiol Sci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"51","DOI":"10.4161\/derm.24494","article-title":"Sunlight and Vitamin D: A global perspective for health","volume":"5","author":"Wacker","year":"2013","journal-title":"Dermatoendocrinol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00697","article-title":"Vitamin D in Autoimmunity: Molecular Mechanisms and Therapeutic Potential","volume":"7","author":"Dankers","year":"2016","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N Engl J Med"},{"key":"B36","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.jsbmb.2018.09.003","article-title":"The serum vitamin D metabolome: What we know and what is still to discover","volume":"186","author":"Tuckey","year":"2019","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvz038","article-title":"Vitamin D: Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level","volume":"4","author":"Bikle","year":"2020","journal-title":"J Endocr Soc"},{"key":"B38","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jsbmb.2013.10.012","article-title":"The role of CYP11A1 in the production of vitamin D metabolites and their role in the regulation of epidermal functions","volume":"144","author":"Slominski","year":"2014","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-020-00913-6","article-title":"Photoprotective Properties of Vitamin D and Lumisterol Hydroxyderivatives","volume":"78","author":"Slominski","year":"2020","journal-title":"Cell Biochem Biophys"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-208975","article-title":"In\u00a0vivo evidence for a novel pathway of vitamin D(3) metabolism initiated by P450scc and modified by CYP27B1","volume":"26","author":"Slominski","year":"2012","journal-title":"FASEB J"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.12.012","article-title":"In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland","volume":"383","author":"Slominski","year":"2014","journal-title":"Mol Cell Endocrinol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jsbmb.2014.11.010","article-title":"Novel activities of CYP11A1 and their potential physiological significance","volume":"151","author":"Slominski","year":"2015","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/srep14875","article-title":"Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland","volume":"5","author":"Slominski","year":"2015","journal-title":"Sci Rep"},{"key":"B44","doi-asserted-by":"publisher","first-page":"11434","DOI":"10.1038\/s41598-017-10202-7","article-title":"Characterization of a new pathway that activates lumisterol in vivo to biologically active hydroxylumisterols","volume":"7","author":"Slominski","year":"2017","journal-title":"Sci Rep"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/exd.14170","article-title":"COVID-19 and Vitamin D: A lesson from the skin","volume":"29","author":"Slominski","year":"2020","journal-title":"Exp Dermatol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.638621\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T09:16:25Z","timestamp":1614244585000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2021.638621\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":45,"alternative-id":["10.3389\/fendo.2021.638621"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2021.638621","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,25]]},"article-number":"638621"}}