Pharmacogenomics of COVID-19 Therapies

Pharmacogenomics seeks to elucidate how inherited genetic variation influences individual responses to antiviral agents, immunomodulators and supportive treatments deployed against COVID-19. During the pandemic, a broad spectrum of repurposed drugs—including nucleotide analogues, protease inhibitors, antimalarials and monoclonal antibodies—has been administered under emergency use protocols. Substantial interindividual variability in therapeutic efficacy, risk of toxicity and incidence of adverse drug reactions has emerged, driven in part by genetic polymorphisms in drug-metabolising enzymes, transporters and immune-related pathways. Integration of genotype data with pharmacokinetic and pharmacodynamic profiles has enabled the identification of actionable gene–drug pairs, such as cytochrome P450 variants affecting remdesivir metabolism and transporter polymorphisms modulating hydroxychloroquine clearance. Advances in machine learning and network-based modelling are refining predictions of drug–drug interactions and off-target effects in complex regimens. Ultimately, embedding pharmacogenomic screening within clinical trials and real-world treatment guidelines holds promise to optimise dosing, mitigate serious adverse events and accelerate the delivery of precision therapies in both acute and long-COVID settings worldwide.

Research from Nature Portfolio

Innovative computational approaches have been applied to predict side-effect profiles and drug–drug interactions among candidate therapies for COVID-19. In particular, graph convolutional network models have been used to map interactions between eight COVID-19 drugs and hundreds of co-administered agents, revealing a heightened risk of haematopoietic and cardiovascular toxicities when certain antivirals are combined. The analysis identified heparin and atazanavir as having the greatest potential to induce adverse events in key organ systems, emphasising the need for algorithm-guided selection of drug combinations to reduce iatrogenic harm in polypharmacy settings.

Pharmacogenomics of COVID-19 Therapies publication trend

The graph below shows the total number of articles in pharmacogenomics of covid-19 therapies across all publications each year (not limited to Nature Index journals).

Technical terms

Pharmacogenomics: The study of how genetic variation affects drug response and safety, integrating genomics with pharmacology.

Cytochrome P450 enzymes: A family of liver enzymes responsible for the metabolism of endogenous compounds and xenobiotics, including many COVID-19 therapies.

Drug–drug interaction: A modification of the effect of one drug by the presence of another, often via shared metabolic pathways or transporter competition.

Genetic polymorphism: A common variation in DNA sequence among individuals that can alter gene function or expression.

Pharmacokinetics: The branch of pharmacology that studies the absorption, distribution, metabolism and excretion of drugs.

Pharmacodynamics: The study of the biochemical and physiological effects of drugs and their mechanisms of action.

Precision medicine: A clinical approach that uses individual genetic, environmental and lifestyle information to optimise therapeutic decisions.

References

1. Pharmacogenomics of COVID-19 therapies. npj Genomic Medicine (2020).
2. Pharmacogenetics Approach for the Improvement of COVID-19 Treatment. Viruses (2021).
3. The Role of Cytochrome P450 Enzymes in COVID-19 Pathogenesis and Therapy. Frontiers in Pharmacology (2022).
4. Identifying side effects of commonly used drugs in the treatment of Covid 19. Scientific Reports (2020).