Targeting patients for early COVID-19 therapy; Pre-infection metabolic dysfunction, polycystic ovary syndrome and risk of severe disease in patients under 65: A Massachusetts community-based observational study

INTRODUCTION: The demographics of those developing severe coronavirus disease (COVID-19) outcomes are shifting to younger patients. In an observational study utilizing electronic health records from a Massachusetts group medical practice, we identified 5025 patients with confirmed COVID-19 from March 1 to December 18, 2020. Of these, 3870 were under 65 years of age. We investigated the hypothesis that pre-infection metabolic or immunologic dysregulation including polycystic ovary syndrome (PCOS) increased risk of serious COVID-19 outcomes in patients under 65 years of age. MATERIALS AND METHODS: We compared those with COVID-19 related hospitalization or mortality to all other COVID-19 patients, using a case control approach. Using logistic regression and propensity score modeling, we evaluated risk of developing severe COVID-19 outcomes (hospitalization or death) in those with pre-infection comorbidities, metabolic risk factors, or PCOS. RESULTS: Overall, propensity score matched analyses demonstrated pre-infection elevated liver enzymes alanine aminotransferase (ALT) >40, aspartate aminotransferase (AST) >40 and blood glucose ≥215 mg/dL were associated with more severe COVID-19 outcomes, OR = 1.74 (95% CI 1.31, 2.31); OR = 1.98 (95% CI 1.52, 2.57), and OR = 1.55 (95% CI 1.08, 2.23) respectively. Elevated hemoglobin A1C or blood glucose levels were even stronger risk factors for severe COVID-19 outcomes among those aged < 65, OR = 2.31 (95% CI 1.14, 4.66) and OR = 2.42 (95% CI 1.29, 4.56), respectively. In logistic regression models, women aged < 65 with PCOS demonstrated more than a four-fold increased risk of severe COVID-19, OR 4.64 (95% CI 1.98, 10.88). CONCLUSION: Increased risk of severe COVID-19 outcomes in those < age 65 with pre-infection indicators of metabolic dysfunction heightens the importance of monitoring pre-infection indicators in younger patients for prevention and early treatment. The PCOS finding deserves further investigation. Meanwhile women who suffer from PCOS should be carefully evaluated and prioritized for earlier COVID-19 treatment and vaccination.