Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study

Abstract

Background. The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. Methods. Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. Results. The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). Conclusions. Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study

“…This present analysis follows in the footsteps of tentative evidence derived from a recent prospective study [ 30 ] and three clinical trials [ 31 , 32 , 33 ], two of which have shown benefit (one did not observe any effect) in patients hospitalized with COVID-19 following vitamin D supplementation.…”

“…In the quasi-experimental prospective study by Annweiler and colleagues, patients hospitalized for proven COVID-19 were stratified into three groups: Group 1, in which vitamin D was regularly supplemented during the 12 months prior to diagnosis; Group 2 in which vitamin D was given soon after hospital admission and Group 3, in which patients were not treated with vitamin D. Those who were supplemented with vitamin D after a diagnosis of COVID-19 did not show any significant benefit compared to untreated controls [ 30 ]. Instead, patients who regularly received bolus vitamin D3 supplementation in the preceding 12 months experienced a significantly lower mortality rate over 14 days (HR: 0.07, p = 0.017) compared to the control group (without vitamin D).…”

“…Although the benefit of supplementary vitamin D in patients with COVID-19 remains speculative and partially supported by limited data from observational studies [ 30 ] and three clinical trials [ 31 , 32 , 33 ], the real-life impact of vitamin D supplementation in patients infected with COVID-19 on outcome in Italy are still not available, particularly in elderly fragile patients with underlying comorbid diseases, who are at greatest risk for more severe clinical outcomes [ 34 ]. Furthermore, several studies evaluating the effect of vitamin D on COVID-19 patients have been limited by the low dose administered [ 30 , 31 ] or because patient characteristics may have precluded the possibility to observe a measurable effect of treatment [ 31 ]. The use of high-dose (~500,000 IU) cholecalciferol has already been shown to reduce hospital mortality in critically ill patients who were severely deficient in vitamin D [ 35 ], however, few studies have examined the effect of high-dose cholecalciferol in COVID-19 patients.…”

Investigating the Potential for Ultraviolet Light to Modulate Morbidity and Mortality From COVID-19: A Narrative Review and Update

“…When the effects of standard care with and without oral calcifediol [25(OH)D; 0.532 mg on day of admission, 0.266 mg on days 3 and 7 then weekly] were compared in 76 people admitted to a Spanish hospital for COVID-19, reduced risk for admission to intensive care was observed for those treated with calcifediol (OR 0.03, 95% CI 0.003–0.25, after adjusting for prevalence of hypertension and type-2 diabetes) ( 264 ). From two “quasi-experimental” French studies, regular supplementation with “bolus” vitamin D [e.g., 80,000 IU vitamin D every 2–3 months ( 265 )] prior to disease onset, reduced the risk of death from COVID-19 in both hospitalized patients [ n = 77: HR 0.07 95% CI 0.01–0.61 ( 266 )], and people living in a nursing home [ n = 66: HR 0.11 95% CI 0.03–0.48 ( 265 )] with models adjusted for age, gender and other factors. A limitation of these studies was that not all SARS-CoV-2 infections were confirmed by PCR.…”

Determination of interest in vitamin use during COVID-19 pandemic using Google Trends data: Infodemiology study

“…There are studies demonstrating that COVID-19 patients have lower vitamin D levels with average plasma concentrations about half that of controls. Therefore, vitamin D supplementation is recommended to improve immunity against COVID-19 and reduce human deaths [32] , [33] , [34] , [35] , [36] .…”