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

Results from this retrospective analysis demonstrate that two consecutive doses of 200,000 IU cholecalciferol (total of 400,000 IU) can significantly improve the outcome in patients affected by COVID-19 that are also burdened with three or more comorbid diseases.

Ninety-one patients (50 males and 41 females aged 40–98 years; mean age 74 years) consecutively admitted from the emergency department in the internal medicine ward specifically dedicated to the management of COVID-19 patients in the University Hospital of Padova, Italy, from 15th March to 20th April 2020 were included. All participants included in this study had: 

• a confirmed diagnosis of COVID-19 infection according to the WHO, by a positive result of real-time reverse transcriptase PCR (RT-PCR) assay;  
• age of 40 or more years;  
• the presence on admission of fever (body temperature of 37.5 °C), interstitial lung pattern or consolidation on chest X-ray and dyspnea;  
• testing of serum 25(OH) vitamin D levels within 24 h of admission; and 
• fully available data on the specific treatment applied, including in-hospital cholecalciferol administration. 

Patients were followed for the duration of their in-hospital stay or until death. 

• Over the follow-up period 27 (29.7%) patients were transferred to the ICU and 22 (24.2%) died (16 prior to ICU and six in ICU). Overall, 43 (47.3%) patients experienced the combined endpoint of transfer to ICU and/or death.  
• Additional analyses revealed that the presence of multiple medical conditions (i.e., the comorbidity burden) significantly modified the effect of vitamin D treatment on the study outcome. The positive effect of high-dose cholecalciferol supplementation on reducing ICU admission or death was significantly amplified with increasing comorbidity burden.

• Observational studies involving databases that are retrospectively examined may be characterized by a lack of reliability of results and incompleteness of data. 
• This study included patients from a single center in Northern Italy and may not be generalizable to all COVID-19 patient populations. 
• The study included a very limited number of patients (n=91) and no formal sample size calculation was performed. 
• Because a post-dose measurement of serum 25(OH)D was not performed, the effectiveness of supplementation to increase vitamin D levels could not be assessed. 

Results from this retrospective analysis demonstrate that two consecutive doses of 200,000 IU cholecalciferol (total of 400,000 IU) can significantly improve the outcome in patients affected by COVID-19 that are also burdened with three or more comorbid diseases. These findings are hypothesis generating and as such should be treated with caution. 

Retrospective analysis 

• Based on the individual clinical judgement of the referring physician, patients were administered 400,000 IU vitamin D supplementation as bolus oral cholecalciferol (two vials of 100,000 IU) daily for two consecutive days (the second and third day of the in hospital stay). Following this treatment decision, patients were divided into two groups depending on whether they received cholecalciferol (n = 36; 47% female) or not (n = 55; 44% female). 
• The decision to administer vitamin D was largely based on: 
  • low (<50 nmol/L) 25(OH) vitamin D, 
  • current cigarette smoking,  
  • elevated D-dimer levels, and  
  • the presence of comorbid diseases, the most frequent of which were cardiovascular disease (79%) and diabetes (33%).
• Computerized medical records were reviewed and demographic, clinical, radiological and laboratory data were collected at admission. These included the following: age, sex, body mass index (BMI), comorbidities (cardiovascular diseases (CVDs), diabetes mellitus, chronic obstructive pulmonary disease (COPD), endocrine diseases, CKD, active cancer, hematological diseases), current smoking status, vital signs, including pulse oxygen saturation (SpO2%), and, among a range of laboratory tests, serum 25(OH) vitamin D, serum calcium and phosphate, serum creatinine, serum C-reactive protein (CRP), serum procalcitonin (PCT), lactate dehydrogenase (LDH) and D-dimer. Partial pressure of oxygen (PaO2), fraction of inspired oxygen (FiO2) and their ratio (PaO2/FiO2) on arterial blood gas (ABG) were also collected.

Giannini, S., Passeri, G., Tripepi, G., Sella, S., Fusaro, M., Arcidiacono, G., Torres, M. O., Michielin, A., Prandini, T., Baffa, V., Aghi, A., Egan, C. G., Brigo, M., Zaninotto, M., Plebani, M., Vettor, R., Fioretto, P., Rossini, M., Vignali, A., Fabris, F. and Bertoldo, F. (2021) ‘Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study’, Nutrients, 13(1).