COVID-19 and long-term risk of incident laboratory-defined micronutrient deficiency in patients with type 2 diabetes: a multicenter propensity score-matched cohort study.

BACKGROUND: COVID-19 has been linked to broad post-acute sequelae, but delayed micronutrient deficiency remains insufficiently characterized. Whether COVID-19 increases long-term risks of laboratory-defined vitamin D, magnesium, and vitamin B12 deficiencies among patients with type 2 diabetes mellitus is unclear. METHODS: Using the predominantly US-based TriNetX network, we identified adults with type 2 diabetes mellitus (T2DM) during 2020-2022 who had COVID-19 and matched controls without COVID-19. A 12-month landmark design excluded pre-existing deficiencies, skeletal outcomes, and early deaths. After 1:1 propensity score matching, Cox models estimated hazard ratios (HRs) for incident deficiencies and skeletal outcomes over an up-to-5-year analytic window, with tested-cohort, severity-gradient, competing-risk, and E-value analyses. RESULTS: After matching, 645,168 patients remained per group. COVID-19 was associated with higher risks of vitamin D deficiency (HR, 1.79), magnesium deficiency (HR, 1.77), vitamin B12 deficiency (HR, 1.56), osteoporosis (HR, 1.55), osteoporotic fracture (HR, 1.73), femur fracture (HR, 1.58), and death (HR, 1.59; all p < 0.001). Among patients with corresponding nutrient testing, risks remained higher for vitamin D deficiency (19.1% vs. 12.8%, HR, 1.68), magnesium deficiency (25.1% vs. 20.0%, HR, 1.47), and vitamin B12 deficiency (4.4% vs. 3.4%, HR, 1.42, all p < 0.001). In tested cohorts, cumulative-incidence estimates remained higher after COVID-19 despite greater competing mortality. Risks were generally higher after severe infection. CONCLUSION: In patients with T2DM, COVID-19 was associated with increased long-term risks of laboratory-defined micronutrient deficiencies and skeletal outcomes. These hypothesis-generating findings warrant prospective confirmation.