Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19

Vitamin D and calcium deficiency may be related to short-term COVID-19 outcomes and therefore it may improve outcomes to screen and address levels of vitamin D and calcium during treatment.  The study authors recommend further study using randomized controlled trials to evaluate the effects of vitamin D and calcium supplementation and confirm this preliminary hypotheses, which was drawn from an observational study.  

120 patients (69% males, mean age 62.3) with severe cases of diagnosed COVID-19 admitted to a single center in Algeria from July, 6 to August 14, 2020.

• Approximately three-quarters of enrolled patients had an inadequate 25 (OH) D level, distributed as follows: vitamin D insufficiency (19.2%), vitamin D deficiency (29.2%), and severe vitamin D deficiency (26.7%).  
• Hypocalcemia on admission was also very common as only 35.8% of patients admitted had adequate levels of corrected serum calcium.  
• During their follow-up, about 25% of the patients developed an AKI, 19.2% developed a cardiac injury and 30.8% of them did not survive.  
• The mean duration between intensive care unit (ICU) admission and death was 7.7 ± 4.7 days, range [03–28] days.  
• The worse the vitamin D status and the worse the calcium levels, the worse the outcomes. This association was independent of other confounding (related) factors with already proven prognostic value such as inflammatory markers (CRP, NLR and neutrophils), AKI, cardiac injury, gender, and age. 

This is a small study from a single center. They did not look at other nutritional deficiencies that may have been related and impacted their findings. 

This study demonstrates the high frequency of hypocalcemia and hypovitaminosis D in severe COVID-19 patients and provides further evidence of their potential link to poor short-term prognosis. It is, therefore, possible that correction of albuminemia, hypocalcemia as well as supplementation with vitamin D may attenuate the severity and improve the vital prognosis. Randomized controlled trials should be conducted to evaluate the effects of this supplementation and to confirm preliminary hypotheses drawn from observational studies.

All patients were assessed for vitamin D status subjects were assigned into one of the following categories based on their total 25 (OH) D levels: optimal: (>78 nmol/l or >30 μg/l), insufficiency (52–75 nmol/l or 20–29 μg/l), deficiency (26–52 nmol/l or 10–20 μg/l) and severe deficiency (<26 nmol/l or <10 μg/l). Serum calcium was also assessed and hypocalcemia was defined as a corrected serum calcium level of less than 2.20 mmol/l . 

In addition to 25 (OH) D and total serum calcium, all patients were tested upon admission for the following laboratory parameters: hypersensitive troponin (hsTrp), inflammatory markers: C-reactive protein (CRP), white blood cells (WBC), neutrophils, lymphocytes, neutrophil to lymphocyte ratio (NLR) and platelets; blood glucose and renal markers: blood urea nitrogen (BUN), serum creatinine (Scr); nutritional markers: serum albumin, total protein, and total cholesterol (TC); liver enzymes: lactate dehydrogenase (LDH), glutamo-oxaloacetic transaminase (GOT) glutamo-pyruvic transaminase (GPT), γ-glutamyl-transpeptidase (GGT), and alkaline phosphatases (ALP). 

Acute kidney injury (AKI) was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines by an increase in serum creatinine of 26.5 μmol/l (03 mg/l) within 48 hours or at least a 50% increase in serum creatinine over 7 days. Cardiac injury was defined based on the hsTrp Kit by an hsTrp >100 ng/l or an increase of more than 30% of the baseline value. 

Bennouar S, Cherif AB, Kessira A, Bennouar DE, Abdi S. Vitamin D Deficiency and Low Serum Calcium as Predictors of Poor Prognosis in Patients with Severe COVID-19. J Am Coll Nutr. 2021 Feb;40(2):104-110. doi: 10.1080/07315724.2020.1856013. Epub 2021 Jan 12. PMID: 33434117; PMCID: PMC7814570. https://pubmed.ncbi.nlm.nih.gov/33434117/