Low Vitamin D Status at Admission as a Risk Factor for Poor Survival in Hospitalized Patients With COVID-19: An Italian Retrospective Study

Study participants were 137 patients who were admitted to a hospital in Rome Italy between March 1 and April 30, 2020 with COVID-19 who had serum 25(OH)D levels < 75 nmol/L, suggesting a possible role of low vitamin D status in increasing the risk of SARS-CoV-2 infection and subsequent hospitalization. The association between low serum 25(OH)D levels and increased risk of in-hospital mortality observed in the study group suggests that a lower vitamin D status upon admission may represent a modifiable and independent risk factor for poor prognosis with COVID-19.

One-hundred thirty-seven consecutively admitted COVID-19 positive patients with  available data on serum vitamin D [25(OH)D] levels, who were admitted to Tor Vergata University Hospital-PTV, Rome, Italy during the study period. All patients had laboratory confirmed cases of COVID-19, were Caucasian and resided in the Lazio region of Italy. 

March 1, 2020 and April 30, 2020 

• Of the 137 COVID-19 patients, 57% survived (n=78) and 43% died (n=59). 
• The survivor group was significantly younger than the non-survivor group (mean age=65 ± 13 years vs 70 ± 14 years, respectively). 
•  The non-survivor group had a significantly higher percentage of men (78%; n=46) than the survivor group (55%; n=43). 
• Median BMI values between survivors and non-survivors were comparable. However, the percentage of obese patients (defined as a BMI value of ³30 kg/m2) was significantly higher in non-survivors compared to survivors (29% vs 15%; n=17 vs 12).  
• Among survivors, 35% had hypertension and/or CVD (n=27), 10% had diabetes mellitus (n=8) and 9% had active or previous malignancy (n=7). Among non-survivors, 42% had hypertension and/or CVD (n=25), 10% had diabetes mellitus (n=6) and 15% had active or previous malignancy (n=9). There was no statistically significant difference in the percentage of hypertension and/or CVD, diabetes mellitus and active or previous malignancy between survivors and non-survivors. 
• Total median serum 25(OH)D levels at admission were significantly higher in survivors than non-survivors (30 nmol/L vs 20 nmol/L).  
• After adjusting for major confounders (age, sex, obesity, neutrophil-to-lymphocyte count ratio (NLR), fibrinogen, D-dimer), there was a significant association between low serum 25(OH)D levels and greater risk of COVID-19 in-hospital mortality.  
• Non-survivors exhibited significantly higher median levels of inflammation and immune system activity such as white blood cell (WBC) count, NLR, high-sensitivity C-reactive protein (hsCRP), ferritin, interleukin 6 (IL-6), D-dimer, fibrinogen and procalcitonin (PCT) compared to survivors at three different time points during hospitalization. 
• The best predictive biomarkers for poor prognosis of COVID-19 were hsCRP, NLR, ferritin and D-dimer. IL-6, PCT, fibrinogen, 25(OH)D, WBC count and tumor necrosis factor alpha (TNF-a) may serve as supportive biomarkers for worse clinical course of the disease. 

Major limitations of the present study, include: 

• The retrospective database design, 
• Small sample size,  
• Lack of information on chronic lung disease,  
• Lack of a healthy (non-COVID infected) control group, and 
• Its single-center setting, which does not allow generalization to other populations. 

A high prevalence of hypovitaminosis D was found in patients hospitalized with COVID-19 in Italy, suggesting a possible role of low vitamin D status in increasing the risk of infection and subsequent hospitalization. Non-survivors exhibited significantly lower vitamin D levels at admission compared to survivors, as well as higher levels of markers of inflammation, coagulation and sepsis. Serum 25(OH)D levels were significantly inversely associated with the risk of COVID-19 in–hospital mortality, independent of age, sex, markers of inflammation, coagulation and sepsis, and major comorbidities.

• This was a retrospective, single-center study.  
• All patients received the same standard care for the treatment of COVID-19 (as per institutional protocol) consisting of a combination therapy with dexamethasone plus hydroxychloroquine and lopinavir/ritonavir administered shortly after admission.  
• The 137 participants included 89 males (65%) and 48 females (35%). 
• None of the patients reported vitamin D supplementation prior to hospital admission. 
• At admission, all 137 patients showed low vitamin D (hypovitaminosis), defined as serum 25(OH)D levels <75 nmol/L according to the Endocrine Society guidelines on evaluation, treatment and prevention of vitamin D deficiency. 
• The primary outcomes measured were survival and death. Data regarding hospital length of stay and intensive care unit length of stay were also collected. 

Infante M, Buoso A, Pieri M, Lupisella S, Nuccetelli M, Bernardini S, Fabbri A, Iannetta M, Andreoni M, Colizzi V, Morello M. Low Vitamin D Status at Admission as a Risk Factor for Poor Survival in Hospitalized Patients With COVID-19: An Italian Retrospective Study. J Am Coll Nutr. 2021 Feb 18:1-16. doi: 10.1080/07315724.2021.1877580. Epub ahead of print. PMID: 33600292; PMCID: PMC7899172. https://pubmed.ncbi.nlm.nih.gov/33600292/