Vitamin D deficiency in critically ill COVID-19 ARDS patients

In this single-center retrospective study of 26 COVID-19 patients in Germany with acute respiratory distress syndrome (ARDS) who received intensive care, a majority had vitamin D deficiency (22 patients, 84.6%). Low vitamin D status was not related to changes in type and severity of symptoms, however low levels of vitamin D (<20 pg/ml) was associated with prolonged mechanical ventilation and duration of ICU treatment.

• All patients without prior vitamin D supplementation (n=22) had 25-hydroxyvitamin D levels below 30 ng/ml (<75 nmol/l), whereas eight patients were severely deficient with levels below 12 ng/ml (<30 nmol/l).
• 1,25-dihydroxyvitamin D had a median value of 27.5 pg/ml on admission and was not below the reference range.
• After vitamin D supplementation, 25-hydroxyvitamin D levels significantly increased. However, median levels were still insufficient (<30 ng/ml or 75 nmol/l). Vitamin D supplementation did not lead to an overall increase in 1,25-dihydroxyvitamin D after 10-15 days
• After 10-15 days, clinical parameters did not differ between patients with sufficient and insufficient or deficient levels of 25-hydroxyvitamin D, respectively.
• Patients with 1,25-dihydroxyvitamin D <20 pg/ml tended to require significantly longer mechanical ventilation and duration of ICU treatment with higher acute physiology and chronic health evaluation (APACHE) II scores.
• Levels of immune cells and pro- and anti-inflammatory cytokines did not differ as a function of vitamin D levels with the only exception being circulating plasmablasts. Circulating plasmablasts were significantly higher in patients with 25-hydroxyvitamin D levels ³30 ng/ml.

Included in this study were 26 patients (17 men, 65%; 9 women, 35%) with confirmed SARS-CoV-2 infection who were hospitalized in Germany between March 14, 2020 and May 28, 2020 with acute respiratory distress syndrome (ARDS) and were treated in the intensive care unit (ICU). All patients had measurements of serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D on admission as well as after 10-15 days of ICU care. Mean age was 59.5 years ranging from 51-69 years. Ninety-six percent of the patients suffered from severe COVID-19 ARDS.

Limitations of the study include:

• The limited number of patients. A larger sample size would increase the power and robustness of the study.
• A minority of patients replenished their vitamin D storage within the observation period and became vitamin D sufficient. This was most likely due to short follow-up time or and inadequate dose regime.
• The lack of a control group of patients without vitamin D supplementation.
• Missed sampling during the initial disease phase as the majority of patients were referred for intensive care treatment.
• This study included patients from a single center in Germany and may not be generalizable to all COVID-19 patient populations.

Most COVID-19 ARDS patients in this study had vitamin D deficiency (22 patients, 84.6%). 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D (<20 pg/ml) were associated with prolonged mechanical ventilation and duration of ICU treatment with higher acute physiology and chronic health evaluation (APACHE II) scores.

• This was a single-center retrospective study of patients at the University Hospital Wuerzburg, Germany with a confirmed SARS-CoV-2 infection and COVID-19 ARDS who received intensive care between March 14, 2020 and May 28, 2020.
• Prior medical history was evaluated based on written records and clinical parameters were extracted from the patient data management system.
• COVID-19 ICU standard care included the administration of 200,000 IU vitamin D3 as a loading dose and 10,000 IU daily via enteral feeding.
• 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days of ICU care.
• Serum 25-hydroxyvitamin D levels of <30 ng/ml (<75 nmol/l) were classified as insufficient and <20 ng/ml (<50 nmol/l) as deficient. Severe vitamin D deficiency was defined as 25-hydroxyvitamin D levels <12 ng/ml (<30 nmol/l). For 1,25-dihydroxyvitamin D, levels below <20 pg/ml were considered deficient.

Notz Q, Herrmann J, Schlesinger T, Kranke P, Sitter M, Helmer P, Stumpner J, Roeder D, Amrein K, Stoppe C, Lotz C, Meybohm P. Vitamin D deficiency in critically ill COVID-19 ARDS patients. Clin Nutr. 2021 Mar 7:S0261-5614(21)00135-7. doi: 10.1016/j.clnu.2021.03.001. Epub ahead of print. PMID: 33745749; PMCID: PMC7937427.