Pharmacogenomics in the time of COVID-19: Preemptive testing and ADRs in hospitalized patients
The COVID-19 pandemic has affected the world in unprecedented ways, and we are continually learning how this virus affects our present and future realities. One of the things that has become clear is that reactive approaches to healthcare may not suffice, and that preventative measures are an important part of patient care.
In a general sense, pharmacogenomics (PGx) can be used as a preemptive tool to help providers optimize medication decisions for individual patients. Providers can use their patient’s PGx results to determine which medication may work well for him or her, reduce adverse drug reactions, minimize medication trial and error, and save the patient time and money.
When it comes to COVID-19, pharmacogenomics can be of value, specifically in helping providers reduce the likelihood of adverse drug reactions (ADRs) in patients hospitalized with the virus.
Polypharmacy and ADR risk
Generally speaking, the incidence of ADRs in hospitalized patients is approximately 17%.1 Critical hospital patients are considered a high-risk group for ADRs because of the multiple high alert medications used and the associated medical complexity. It has been described that the incidence of ADR in ICU patients is 20%, and 13% will be a fatal or life-threatening scenario.2 Imagine the value of having pharmacogenomic information readily available for patients before hospitalization.
Polypharmacy in COVID-19 patients
When it comes to this pandemic, it has been reported that up to 20% of SARS-CoV-2 (COVID-19)infected patients may require hospitalization.3 Patients hospitalized with COVID-19 can be candidates for receiving several treatments that aim to maintain tissue and organ function balance, improve lung function, and/or control virus invasion, anti-hypoxic, anti-septic shock, and anti-secondary infection. They may also receive specific treatments for preexisting health conditions.4
The majority of COVID-19 related inpatients are elderly individuals with preexisting polypharmacy. In the U.S., the most common multidrug combinations are for treating manifestations of metabolic syndrome, and 61% of adults over 65 years of age had two or more chronic conditions.5 As a result, metabolic conditions are also the biggest comorbidities in terms of COVID-19 disease.6 Therefore, the potential impact of ADRs on the outcome of patients diagnosed with COVID-19 must be considered, and those ADRs should be prevented, if possible.
Pharmacogenomics may help
Several factors can contribute to how an individual may respond to a medication.The individual’s genetic makeup is one of those factors, and it is widely accepted that pharmacogenomics can play a role in helping providers make more informed medication decisions for their patients.
Commonly described ADRs in COVID-19 inpatients are cardiovascular in nature, such as long QT syndrome and torsades de pointes.7 Pharmacogenomic testing may play a role in helping providers reduce the risk of these ADRs for COVID-19 patients.
For example, some of the medications being explored as experimental COVID-19 treatments - like chloroquine, hydroxychloroquine, lopinavir/ritonavir and azithromycin - can be related to an increased risk for ADRs. There is strong evidence for gene-drug interactions between some of those medications and genes such as CYP2D6, CYP2C8, 6GPD (for chloroquine, hydroxychloroquine), and CYP3A4 (for lopinavir/ritonavir).
Additionally, COVID-19 patients are likely to require adjuvant therapies as part of their treatment, and several of those therapies have a well known, clinically relevant gene-drug interaction such as CYP2D6 and ondansetron (LOE 1A, CPIC Guideline available), CYP2C19 and citalopram (LOE 1A, FDA recommendations available), CYP2D6 and codeine (LOE 1A, CPIC Guideline available) and CYP3A4 and fentanyl (LOE 2A, PharmGKB), among others.
With the help of their patient’s pharmacogenomic test results, providers may determine preemptively how that patient could respond to certain medications and potentially minimize ADRs for him or her.
History has taught us that significant changes, innovations, and improvements often arrive during times of crisis. Perhaps the current pandemic will help us realize the value of preemptive pharmacogenomic testing for patient care.
References1 Moore P., Burkhart K. (2017) Adverse Drug Reactions in the Intensive Care Unit. In: Brent J. et al. (eds) Critical Care Toxicology. Springer, Cham>
2 Rothschild J.M., Landrigan C.P., Cronin J.W., Kaushal R., Lockley S.W., Burdick E., Stone P.H., Lilly C.M., Katz J.T., Czeisler C.A., & Bates D.W. (2005). The Critical Care Safety Study: the incidence and nature of adverse events and serious medical errors in intensive care. Crit Care Med. 33(8):1694–700. doi: 10.1097/01.CCM.0000171609.91035.BD
3World Health Organization. (2020). Coronavirus disease (COVID-19) Pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019
4Liu Y., Yan L.M., Wan L., Xiang T.X., Le A., Liu J.M., Peiris M., Poon L.L.M., & Zhang W. (2020, March 19). Viral Dynamics in the mild and severe cases of COVID-19. The Lancet. Doi: 10.1016/S1473-3099(20)30232-2
5 Payne R. A. (2016). The epidemiology of polypharmacy. Clinical medicine (London, England), 16(5), 465–469. Doi: 10.7861/clinmedicine.16-5-465
6 Zhou F., Yu T., Du R., Fan G., Liu Y., Liu Z., Xiang J., Wang Y., Song B., Gu X., Guan L., Wei Y., Li H., Wu X., Xu J., Tu S., Zhang Y., Chen H., & Cao B.(2020, March 11). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Doi: 10.1016/S0140-6736(20)30566-3
7 PharmGKB. (2020, May 11). Therapeutic Resource for COVID-19. PharmGKB. https://www.pharmgkb.org/page/COVID