The role of DPYD testing in managing a successful response to the COVID-19 pandemic – 5 November 2020

Since the beginning of the global COVID-19 outbreak, the diagnostic and research community has undertaken an unprecedented effort to understand how best to manage, eradicate and prevent the disease. Two key pillars in the fight against the pandemic are establishing a robust testing strategy and implementing procedures and processes to reduce the burden on healthcare systems.  

Independent SAGE recently published a document containing core recommendations for how best to optimize and develop the current testing environment (1). It is clear that a wider reaching, more efficient testing strategy is desperately needed – in the UK Baroness Harding (head of NHS Test and Trace) recently briefed the science and technology committee that the number of individuals looking to book a test was three to four times the capacity of the service (2). Outside of the centralised testing systems employed by most Governments across the world, many businesses keen to bring staff back into the workplace have turned to private health companies to meet demand. Other sectors, including universities and independent schools, have also contributed to demand for private testing being thirty times higher than that seen in the summer (3). Facilities have responded in kind, with some creating ‘pop up’ facilities to facilitate the collecting and processing of extra samples (3). Manufacturers of testing kits have also responded by focusing efforts on maximising the ease and efficiency of testing. One area of innovation has been optimising saliva testing in order to move away from the need for nasopharyngeal swabs, which is labour intensive and usually requires close contact with a healthcare professional. 

Despite the collective effort of both the public and private healthcare sectors to increase capacity and develop the testing pathway, diagnosing and identifying cases remains only one of the pillars needed to protect communities and manage the pandemic.

At the onset of the pandemic countries across the world put in place national initiatives to increase the number of available hospital beds and associated staffing resource. Leishenshan Hospital in Wuhan was one of the hospitals built by China in order to handle the large number of COVID-19 patients. The hospital was built in a record time of just 2 weeks, whilst in the UK 7 critical care hospitals were opened in the space of just over a month. 

Alongside such efforts to expand capacity, healthcare systems have worked to reduce the burden on resources – in particular the demand for intensive care unit (ICU) beds. In many countries the public were asked to stay at home except where absolutely necessary, such as to buy food or care for a vulnerable family member. This not only reduced the spread of COVID-19, but also reduced the number of accidents that are associated with travel. In the Tarragona province of Spain the number of traffic accidents fell by almost 75% (4). Difficult decisions were made around prioritising ICU beds and treatment for those critically ill patients who were most likely to benefit from such intervention (5). However, arguably the intervention with the largest impact was many hospitals making the decision to downscale all out-patient clinics and non-urgent interventions and surgeries. Policies were clear, however, that all cancer treatments and other clinically urgent care should continue unaffected (6). 

This raises the question as to whether there are available strategies that could be implemented to reduce the need for intensive care escalation among patients undergoing cancer treatments or other urgent interventions. Fluorouracil (5-FU) and Capecitabine, a prodrug of 5-FU, are fluoropyrimidine chemotherapy agents used in the treatment of cancer. These drugs form a key component of the chemotherapy regime for colorectal, breast, heapato-pancreato-biliary and many other cancers. These drugs are catabolised by the dihydropyrimadine deyhydrogenase (DPD) enzyme, itself encoded by the DPYD gene. Approximately 3–5% of the European population have a partial DPD enzyme deficiency due to a mutation in the gene (7), and complete enzyme deficiency has also been described. In the US it is reported that up to 8% of the general population have at least a partial deficiency (8). Individuals with a complete deficiency are at risk of life threatening or even fatal chemotherapy toxicity when given 5-FU or Capecitabine. Those with a partial deficiency usually experience gastrointestinal adverse reactions such as prolonged vomiting, as well as haematological effects including a decreased white blood cell count when given therapy at the standard dose. The latter puts patients at risk of serious infection, and a fever is often also reported in those with a partial deficiency. Some studies have shown that almost 25% of patients who are given fluoropyrimidine chemotherapy as a first-line drug experience severe toxicity (9). DPYD testing allows for those with a partial or complete deficiency to be identified, and either a modified dose or alternative therapy given to prevent such adverse reactions. In addition to the clear clinical benefit for the patient, a recent study reported that the average cost of an ICU admission following DPYD toxicity was almost €47,000 per person, and as such that pre-emptive DPYD screening of all patients is a cost-effective strategy (9). Many countries are beginning to recognise the clinical and economic benefit of universal pre-emptive DPYD genotyping. Wales is the first nation in the UK to offer the DPYD test to all patients, with over 400 samples already taken and 6% of patients returning a positive result. All Wales Medical Genomics Service (AWMGS) commenced a pilot phase earlier this year using the Elucigene DPYD assay, which then led to the launch of the nation-wide service (10). Similarly the German Federal Joint Committee, G-BA, the national reimbursement authority in Germany, recently approved reimbursement for DPYD testing across the country. Many countries could benefit from adopting similar approaches, especially in the current climate of extra pressure on ICU resources. 

It is clear that testing has a key role to play in managing a successful response to the COVID-19 pandemic. Alongside continuing to support initiatives that foster a robust viral testing and tracing programme, Governments across the world should look to examples of where other testing, such as DPYD screening, is being used innovatively to reduce the burden on resources of critical importance during the pandemic. 

Click here to find out how Yourgene Health can support your organisation in delivering COVID testing. You can also find out how about our range of genotyping tests, including our CE-marked DPYD assay.

1. Independent SAGE: The complexities of testing for COVID-19: the why, the who and the how

2. Coronavirus: Test demand ‘significantly outstripping’ capacity

3. Private groups race to meet Covid testing demand from UK companies

4. COVID-19 lockdown and reduction of traffic accidents in Tarragona province, Spain

5. Prioritisation of ICU treatments for critically ill patients in a COVID-19 pandemic with scarce resources

6. Covid-19: all non-urgent elective surgery is suspended for at least three months in England

7. DPYD Testing – Manchester University

8. Dihydropyrimidine dehydrogenase deficiency

9. Cost Implications of Reactive Versus Prospective Testing for Dihydropyrimidine Dehydrogenase Deficiency in Patients With Colorectal Cancer: A Single-Institution Experience

10. Elucigene DPYD tests to be used routinely in Wales