Low vitamin D levels are associated with Long COVID syndrome in COVID-19 survivors.

PURPOSE: Long-COVID is an emerging syndrome affecting 50-70% of COVID-19 survivors which still lacks predicting factors. Due to the extra-skeletal effects of vitamin D, we retrospectively assessed in COVID-19 survivors 6-months after hospitalization the association between 25(OH)vitamin D levels and Long-COVID. METHODS: Long-COVID was defined according to NICE-guidelines. Fifty Long-COVID and 50 non-Long-COVID subjects matched on a 1:1-basis were enrolled from an outpatient-post-COVID clinic-cohort seen from August to November 2020. Therapies/comorbidities affecting calcium/vitamin-D/bone metabolism, and/or admission in ICU during hospitalization were exclusion criteria. 25(OH)vitamin D was measured at hospital-admission and 6-months after discharge. RESULTS: We observed lower 25(OH)vitamin D levels, evaluated at follow-up, in subjects with Long-COVID than those without (20.1vs23.2 ng/mL-p = 0.03). Regarding the affected health-areas evaluated in the entire cohort, we observed lower 25(OH)vitamin D levels in those with neurocognitive symptoms at follow-up (n.7) as compared to those without (n.93) (14.6vs20.6 ng/mL-p = 0.042). In patients presenting vitamin D deficiency (<20 ng/mL) both at admission and at follow-up (n.42), those affected by Long-COVID (n.22) presented lower 25(OH)vitamin D levels, at follow-up, compared to those not affected (n.20) (12.7vs15.2 ng/mL-p = 0.041). In multiple-regression analyses, lower 25(OH)vitamin D levels, at follow-up, resulted as the only variable significantly associated with Long-COVID in our cohort (p = 0.008, OR 1.09-CI 1.01-1.16). CONCLUSIONS: COVID-19 survivors with Long-COVID have lower 25(OH)vitamin D levels as compared to matched-patients without Long-COVID. Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital-discharge. Role of vitamin D supplementation as preventive strategy of COVID-19 sequelae should be tested in randomized-controlled trials.

Low vitamin D levels predict outcomes of COVID-19 in patients with both severe and non-severe disease at hospitalization.

PURPOSE: Low vitamin D in COVID-19 have been related to worse outcomes. However, most of the studies conducted so far were not-controlled and retrospective, including biases potentially influencing this association. We evaluated 25(OH)vitamin D levels of patients with both severe and non-severe disease at hospital-admission, and in a cohort of control subjects. Moreover, we evaluated sACE-2 levels to investigate the mechanisms underlying the association between vitamin D and COVID-19. METHODS: COVID-19 patients were enrolled in a matched for age, sex and comorbidities 1:1-ratio based on the presence/or not of respiratory-distress/severe-disease at hospital-admission. Control matched subjects were enrolled from an outpatient-setting. RESULTS: Seventy-three COVID-19 patients (36 severe and 37 non-severe) and 30 control subjects were included. We observed a higher vitamin D deficiency (<20 ng/mL) prevalence in COVID-19 patients than control subjects (75% vs 43%). No differences were found regarding 25(OH)vitamin D and sACE-2 levels between patients with and without severe-disease at study entry. During the disease-course, in the severe group a life-threatening disease occurred in 17 patients (47.2%), and, in the non-severe group, a worsening disease occurred in 10 (27%). 25(OH)vitamin D levels, at admission, were negatively correlated with sACE-2 levels, and were lower in patients whose disease worsened as compared to those in whom it did not, independently from the disease severity at admission. In multivariate-analysis, lower 25(OH)vitamin D resulted as an independent risk factor for disease worsening. CONCLUSIONS: 25(OH)vitamin D levels at hospital-admission strongly predicted the occurrence of worsening outcomes in COVID-19 independently of the disease severity at presentation.