Even if hydroxychloroquine proves to be an effective treatment for COVID-19, the side effects can be deadly. In a recent study, researchers at Uppsala University found a workaround—adjust the dosage of hydroxychloroquine for each patient based on whole blood tests.
While originally developed to treat malaria, hydroxychloroquine has proven effective for systemic lupus erythematosus and rheumatoid arthritis. In fact, it is now recommended to all lupus patients since it protects so well against flares of the disease. However, just as malaria patients have seen, the side effects of hydroxychloroquine, namely heart rhythm problems, are common and can be deadly.
After seeing hydroxychloroquine concentrations vary considerably between individuals with the same dosing regimen, Uppsala researchers developed a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method to accurately measure levels in the blood of lupus patients in a medical setting.
In the study, researchers compared the levels of hydroxychloroquine in plasma, serum and whole blood in 26 lupus patients. The variation between the three matrices was unexpectedly high, with hydroxychloroquine levels in whole blood about twice as high as in serum and plasma.
“One striking result, and a very important insight, was that levels in whole blood for patients prescribed the same dosage could differ by up to 15 times between individuals. This indicates a large individual variation in how the medication is metabolized,” said Kim Kultima, professor at Uppsala University and Uppsala University Hospital, and author of the study.
Thus, after validation and application at both the clinical and laboratory level, researchers concluded that whole blood is the superior matrix and should be used for hydroxychloroquine analysis when patients are monitored for treatment effects.
The LC-HRMS method has been used at Uppsala University Hospital since December 2019. Total chromatographic time is only four minutes, and researchers report it shows good linearity.
“Hydroxychloroquine measurements in routine care can help clinicians motivate patients to improve treatment adherence, and to accordingly adjust doses, avoiding unnecessary addition of potentially more toxic therapy. Monitoring HCQ concentrations could also help minimize the risk of long-term side effects,” the authors write in their study published in Arthritis Research & Therapy.
The researchers caution this analysis method has proven effective in providing the correct dosages to lupus patients only—not COVID-19 patients.
“We have to be very careful about drawing hasty conclusions about whether hydroxychloroquine is effective with COVID-19,” said Kultima.
That being said, those at Uppsala University Hospital do not want to be caught off-guard if hydroxychloroquine does indeed prove effective for COVID-19. Researchers are currently collaborating with doctors at the Infectious Disease Clinic and within intensive care at Uppsala University Hospital to ensure there are plans and preparations in place that would allow them to quickly measure the levels of hydroxychloroquine in the blood of COVID-19 patients should the medication prove fruitful.
to preparations in place to be able to measure the levels of the medication in the blood of COVID-19 patients if the substance proves effective.