Vitamin D Status and Severity of COVID-19

In this Danish observational study of 447 COVID-19 patients, deficient vitamin D levels were associated with an elevated risk of progressing to a more severe COVID-19 outcome. 

• 11%, 30% and 59% of the cohort members had vitamin D deficiency, insufficiency or sufficiency, respectively. 
• Vitamin D level was statistically significantly associated with sex, age, country of origin and comorbidity, but not with obesity or time interval between date of blood sample drawn and SARS-CoV-2 test.
• 68% (145/212) of the cohort members ≥ 70 years had sufficient vitamin D levels versus 50% among individuals <70 years (118/235), and vitamin D sufficiency was more common among individuals with comorbidities than among individuals without comorbidities (68% (115/168) versus 53% (148/279), respectively). 
• Among the 447 cohort members, 126 (28%) were not hospitalized, 205 (46%) were hospitalized for COVID–19, but not admitted to an ICU, 34 (8%) were admitted to an ICU and 82 (18%) died from COVID-19. 
• Lower levels of vitamin D were associated with higher COVID-19 severity among males younger than 65 years of age but not among women of same age. Among the older men and women, the relationship between vitamin D levels and severity of COVID-19 resembled a U-formed association i.e., highest vitamin D levels were observed among those who were not hospitalized and among those who did not survive COVID-19.
• Odds of experiencing more severe COVID-19 among individuals with insufficient (25 to < 50 nmol/L) and sufficient (≥ 50 nmol/L) 25(OH)D levels were approximately 50% of that among individuals with deficient levels (< 25 nmol/L) (POR= 0.49 (95% CI 0.25–0.94), POR= 0.51 (95% CI 0.27–0.96), respectively). 

447 COVID positive patients from the Danish population (Danish nation-wide health registers the COVID-19 surveillance database and stored blood samples from the national biobank).

Some comorbidities may not have been accounted for and since this was a chart review some aspects that may have contributed to deaths and severity of illness may not have been accounted for. The data was gathered at the beginning of the pandemic, in 2020, and may not reflect the results of different strains that have developed since and do not account for how outcomes may be impacted by vaccine status. 

In this Danish observational study of 447 COVID-19 patients, we observed that deficient vitamin D levels were associated with an elevated risk of progressing to a more severe COVID-19 outcome. The possible role of vitamin D supplementation in the treatment of COVID-19 has already been assessed in randomized controlled trials, but as pointed out in recent meta-analyses, large variations in vitamin D supplementation schemes in the hitherto published studies means that no definitive conclusion can be drawn on the therapeutic effect of vitamin D, until larger well-designed interventional studies addressing issues such as the appropriate dose, duration, and mode of vitamin D administration have been completed.

• This large cohort study assessed the association between vitamin D status and COVID-19 severity among Danish COVID-19 patients using the Danish National Patient Registry, the Cancer Registry, the COVID-19 surveillance database, which contains information on all SARS-CoV-2 PCR tests carried out in Denmark, and blood samples stored in the National Biobank. 
• To determine vitamin D status, vitamin D level was calculated as the sum of 25(OH)D3 and 25(OH)D2 from a blood sample collected 1–30 days before registration of a COVID-19 diagnosis was preferred. If this was not possible, a blood sample drawn on the date of registration or 1–2 days after was selected, and if this was not available, the most recent blood sample collected up to 24 months before the COVID-19 registration was used. 
• To confirm the diagnosis of COVID-19, the study cohort was linked to the SSI COVID-19 surveillance database, which includes results for every SARS-CoV-2 PCR test carried out in Denmark since February 2020, it also contains information on hospitalizations, admissions to ICU, and COVID-19 related death. 
• Four categories of increasing COVID severity were defined: (1) no hospital admission (incl. hospital contacts <12 h), (2) hospitalized (≥12 h), but not admitted to ICU, (3) admitted to ICU, regardless of duration of hospital contact and (4) death within 30 days after a positive SARS-CoV-2 test. 
• Confounders such as age, obesity and other illness were identified from the records.
• 25(OH)D levels were defined as, (<25 nmol/L (deficient), 25 to <50 nmol/L (insufficient), and ≥50 nmol/L (sufficient)) and as a continuous variable.

Nielsen, N.M., Junker, T.G., Cohen, A.S. et al. Vitamin D status and severity of COVID-19. Sci Rep 12, 19823 (2022). https://doi.org/10.1038/s41598-022-21513-9