Chronic cholecalciferol supplementation and adequate vitamin D status are associated with reduced risk of Long COVID

Introduction: Vitamin D deficiency has been associated with adverse acute and long-term COVID-19 outcomes. However, data on its supplementation on post-acute recovery are still limited. This retrospective observational study investigated the role of chronic cholecalciferol supplementation and 25(OH) vitamin D concentrations on Long COVID risk. Methods: We included patients with COVID-19 between March 2020 and May 2021 previously followed at our Endocrine Department. Long COVID was defined according to NICE criteria. Patients chronically supplemented with cholecalciferol were compared with matched controls for age, sex, comorbidities, and COVID-19 severity. Results: A total of 132 patients were evaluated; 50 (38%) received cholecalciferol supplementation and 30 (22.7%) developed Long COVID. Long COVID occurred less frequently among supplemented patients (14% vs. 28%, p = 0.086), particularly with daily-doses ≥ 750 IU (12.5% vs. 28.6%, p = 0.051) and ≥ 1000 IU (10.5% vs. 27.6%, p = 0.039). Baseline 25(OH)D concentrations were significantly lower in those with Long COVID (p = 0.02), and showed a significant predictive performance for Long COVID (AUROC 67.3%, p = 0.023). In the matched cohort (n = 86), Long COVID occurred less frequently among supplemented patients (11.6% vs. 32.6%, p = 0.036) and similar findings were confirmed in the matched subgroup receiving ≥ 1000 IU/day (8.5% vs. 34.2%, p = 0.018). Multivariate analyses showed a protective role of cholecalciferol supplementation on Long COVID in both entire and matched cohorts. Conclusions: Chronic cholecalciferol supplementation, particularly at daily doses ≥ 750–1000 IU, was associated with a significantly lower risk of Long COVID. Ensuring adequate vitamin D status may represent a potential useful preventive strategy for post-COVID sequelae.