High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study

In this observational study, treatment with cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19.

A total of 986 in-patients with a clinical diagnosis of COVID-19 recruited from three UK hospitals, of whom 151 (16.0%) received cholecalciferol booster therapy.  

Patients recruited were admitted between January 27, 2020 and August 5, 2020, and data were collected retrospectively between June 26, 2020 and August 7, 2020. 

• Serum 25(OH)D levels were not associated with COVID-19 mortality in either the primary or validation cohort, and deficient vitamin D status (defined as <25 nmol/L) was not associated with COVID-19 mortality in the primary cohort.  
• Treatment with high-dose cholecalciferol booster therapy was associated with a reduced risk of COVID-19 mortality regardless of baseline serum 25(OH)D levels, and this was true in both cohorts. 

• Not all patients had serum 25(OH)D levels available, so the power would have been improved with more values.  
• While the results are potentially generalizable to the UK, similar studies would need to be replicated in different global populations to assess their general validity. 
• Due to the cross-sectional nature of this study, the investigators were unable to ascertain cause and effect between associations and do not have a mechanistic understanding of their findings. A longitudinal analysis of outcomes must be carried out in the future to determine any long-term consequences of deficient vitamin D status during acute COVID-19 infection.  

High-dose cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19. This suggests that further work should be carried out to determine what an adequate serum level of 25(OH)D might be from large-scale population studies, and paves the way for future clinical trials of cholecalciferol therapy, at multiple doses in order to assess maximum efficacy.

• Patients received cholecalciferol booster therapy if they were recognized as being either vitamin D insufficient (serum 25(OH)D 25–50 nmol/L) or deficient as part of routine clinical care. In this study, 151 (16.0%) patients received high-dose cholecalciferol booster therapy (³ 280,000 IU in a time period of up to 7 weeks). 
• Patients were divided into a primary and validation cohort. The primary cohort included 444 subjects enrolled at Tameside General Hospital. The validation cohort was made up of subjects enrolled at both Royal Preston Hospital and University Hospitals of Leicester. The mean ages of the cohorts were ³70 years and included 42.2-57.8 % women. 
• The primary outcome measure, COVID-19 mortality, included deaths in hospital, and deaths following admission recorded during the data collection period, e.g., following transfer or discharge. 
• Logistic regression was used to determine any relationships between COVID-19 mortality and potential predictors, including serum 25(OH)D levels and cholecalciferol booster therapy, with adjustment for the following variables, which are known to be associated with COVID-19 mortality: age, sex, obesity, non-Caucasian ethnicity, and diabetes (types 1 and 2 combined). 

Ling, S. F., Broad, E., Murphy, R., Pappachan, J. M., Pardesi-Newton, S., Kong, M. F. and Jude, E. B. (2020) ‘High-Dose Cholecalciferol Booster Therapy is Associated with  a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre  Observational Study’, Nutrients, 12(12).