By Sharon Oosthoek

A newly developed way to screen for vitamin D deficiency could help critically ill patients stave off hospital acquired infections and reduce the severity of respiratory illnesses such as COVID-19.

Studies show the vitamin has an important role to play in our immune system, fighting off pathogens and reducing harmful inflammation. While the body gets some vitamin D through diet, most of it comes from sunlight exposure.

But Canadian winters, which coincide with respiratory illness season, is when many of us run low on our vitamin D stores, says Philip Britz-McKibbin, a McMaster University analytical chemist who helped develop the new screening tool.

His work is part of an ongoing multicentre clinical trial led by pediatric critical care physician Dayre McNally from the Children’s Hospital of Eastern Ontario. The trial aims to determine the safety and efficacy of high-dose vitamin D supplements to improve children’s recovery following critical illness, including pneumonia, heart surgery and even concussions. Identifying vulnerable children with vitamin D deficiency shortly after critical care admission is a crucial first step.

Not all hospitals routinely do this screening, but when they do, they usually use a immunoassay system, which is essentially an antibody test that binds to 25-hydroxyvitamin D3 – the most abundant circulating vitamin D species in blood. This test is fast, inexpensive and easy to administer, but it suffers from greater measurement variability and is prone to cross-reactivity and bias that may result in vitamin D status misclassification.

The gold standard test, liquid chromatography–tandem mass spectrometry is more precise and accurate, but expensive and slow because it requires separating out the various species of vitamin D from a blood sample before it can be assessed.

Neither test is suited to the high-throughput screening needed to reliably assess large groups of study participants.

“Our main goal was to satisfy a clinical need of a rapid yet accurate method for vitamin D screening that is cost effective, and applicable to fast turn-around assessment in critical care settings or large-scale population screening,” says Britz-McKibbin.

So he and his team developed a new direct infusion-tandem mass spectrometry method that takes advantage of chemo-selective click derivatization and efficient sample cleanup protocol for blood samples.

“All blood samples were extracted and then chemically labeled with a reagent that introduces a positive charge moiety to increase sensitivity in electrospray ionization to allow for low nanomolar detection of major circulating vitamin D species,” says Britz-McKibbin.

The team validated the method to show that it offers better accuracy and precision than a commercial immunoassay, while matching the gold standard liquid chromatography–tandem mass spectrometry test.

The method is described in a paper recently published in The Journal of Lipid Research.

Lars Konermann, a physical chemist at the University of Western Ontario with extensive expertise in mass spectrometry and who was not involved in the research, reviewed the paper. He says the method appears to be well-suited to large-scale studies in nutritional epidemiology, as well as rapid trials on patients who may benefit from vitamin D supplementation.

Britz-McKibbin’s screening tool “allowed hundreds of blood samples to be analyzed within a short time, with excellent reproducibility and lower detection limits compared to traditional methods,” says Konermann.

Karen Choong, pediatric critical care physician at McMaster Children’s Hospital, who co-authored the paper, says having a rapid test to identify vitamin D deficiency is “crucial,” particularly for cases of critically ill children where delays in treatment may affect patient outcomes.

“This test is a major step in ensuring widespread testing is feasible and timely amongst the sickest children admitted to our hospitals,” she says in a news release.