Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

An Integrated Multidisciplinary Circuit Led by Hospital and Community Pharmacists to Implement Clopidogrel Pharmacogenetics in Clinical Practice.

The use of pharmacogenetics to optimize pharmacotherapy is growing rapidly. This study evaluates the feasibility and operability of a collaborative circuit involving hospital and community pharmacists to implement clopidogrel pharmacogenetics in Barcelona, Catalonia, Spain. We aimed to enroll patients with a clopidogrel prescription from cardiologists at the collaborating hospital. Community pharmacists collected patients' pharmacotherapeutic profiles and saliva samples, which were then sent to the hospital for CYP2C19 genotyping. Hospital pharmacists collated the obtained data with patients' clinical records. Data were analyzed jointly with a cardiologist to assess the suitability of clopidogrel. The provincial pharmacists' association coordinated the project and provided IT and logistic support. The study began in January 2020. However, it was suspended in March 2020 due to the COVID-19 pandemic. At that moment, 120 patients had been assessed, 16 of whom met the inclusion criteria and were enrolled in the study. The processing of samples obtained before the pandemic had an average delay of 13.8 ± 5.4 days. A total of 37.5% patients were intermediate metabolizers and 18.8% were ultrarapid metabolizers. No poor metabolizers were detected. Pharmacists rated their experience with a 7.3 ± 2.7 likelihood of recommending that fellow pharmacists participate. The net promoter score among participating pharmacists was +10%. Our results show that the circuit is feasible and operable for further initiatives.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review.

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.Copyright © 2023 Safety and Risk of Pharmacotherapy. All rights reserved.

Trends in molecular diagnostics: 12th European Meeting on Molecular Diagnostics, Noordwijk aan Zee, the Netherlands, 12-14 October 2022.

This report provides an overview of the highlights of the 12th European Meeting on Molecular Diagnostics held in Noordwijk aan Zee, The Netherlands, 12-14 October 2022. This 3-day conference covered many relevant topics in the field of molecular diagnostics in humans i.e. oncology, infectious diseases, laboratory medicine, pharmacogenetics, pathology, and preventive medicine. Other relevant topics included quality management, laboratory automation, diagnostic preparedness, and lessons learned from the COVID pandemic. More than 400 participants, the majority coming from European countries, attended the meeting. Besides high-quality scientific presentations, more than 40 diagnostic companies presented their latest innovations, altogether in an informal and inspiring ambiance.

Safety of Pharmacotherapy in COVID-19 Patients: A Literature Review

The safety of COVID-19 pharmacotherapy is a relevant issue, first of all, because of the current lack of experience with using particular medicinal products and with off-label prescribing. The aim of the study was to analyse information on potential adverse drug reactions (ADRs) and their predictors in etiology- and pathogenesis-oriented COVID-19 therapy. According to literature data, the main clinically significant risk factors for COVID-19 patients to develop an ADR are the duration of their hospital stay, combined use of antivirals, polypharmacy, and their history of drug allergies. The most common adverse reactions to antivirals, to virus-neutralising antibodies, and to human anti-COVID-19 immunoglobulin and convalescent plasma are, respectively, gastrointestinal and hepatobiliary disorders;gastrointestinal disorders, neurological disorders, and allergic reactions;and transfusion reactions (fever, chills, etc.). For pathogenesis-oriented therapy with systemic glucocorticosteroids, the most characteristic ADR is hyperglycaemia. Janus kinase inhibitors and interleukin inhibitors are most often associated with gastrointestinal disorders and hypertransaminasemia;neutropenia is also characteristic of a number of interleukin inhibitors. Haemostatic adverse reactions to anticoagulants depend on the patient's dosing regimen and condition. Drug-drug interactions are a common problem in COVID-19 treatment, with the combination of nirmatrelvir and ritonavir showing the largest number of significant interactions attributed to their pharmacokinetics. Currently, there is data on the role of pharmacogenetic biomarkers in the safety and clinical outcomes of COVID-19 therapy. Thus, to improve the safety of COVID-19 therapy, an integrated approach is needed that will take into account both the clinical, demographic, and pharmacogenetic predictors of ADRs and the risk of drug-drug interactions.

Pharmacogenetics in pharmacy practice: Collaboration between community and hospital pharmacists

Background: Clopidogrel is a CYP2C19-activated pro-drug, used to prevent cardiovascular events. Up to 27% of Caucasians has at least one CYP2C19*2 allele (impaired enzymatic activity), whereas 38% have at least one CYP2C19*17 allele (higher enzymatic activity). However, CYP2C19 pharmacogenetic analysis before prescribing clopidogrel is not widely implemented in clinical practice. Purpose(s): To evaluate feasibility and operability of a collaborative pilot circuit to determine pharmacogenetic markers to optimise clopidogrel prescription. Method(s): The authors expect 150 patients with a clopidogrel prescription by a cardiologist of Hospital de Sant Pau to enrol. They can enrol when filling their prescriptions in one of the 24 collaborating community pharmacies in the Hospital's area. Community pharmacists collect from each participant's pharmacotherapeutic profile and a saliva sample to be sent to the hospital for CYP2C19 genotyping. Hospital pharmacists collate all obtained data with their clinical records. Data are analysed jointly with a cardiologist to assess clopidogrel prescription adequacy. Barcelona Pharmacists' Association (COFB) coordinates the whole project and provides IT and logistic support. Result(s): This project started in January 2020 and it was temporarily suspended due to the COVID19 pandemic. On 13th March 2020, 114 patients with clopidogrel prescriptions were registered, 21 met the inclusion criteria and 15 were enrolled. Five out of the eight already genotyped patients were intermediate or poor metabolisers. Conclusion(s): This circuit seems to be feasible, but further research is needed once the study is resumed. Pharmacogenetics increasing clinical relevance needs more clinical implication of pharmacists.

Evaluation of the association of CES1 (rs2244613) polymorphisms with the safety of remdesivir in hospitalized patients with COVID-19

Introduction. An outbreak of novel COVID-19 infection has become a real challenge for the entire human society, and first of all for the healthcare services. The development of new drugs is a complex and lengthy process. At the beginning of the pandemic, it forced an intensive study of well-known drugs for the therapy. Remdesivir was first investigated as a potential treatment for Ebola virus. After beginning of the COVID-19 pandemic, in vitro evaluations demonstrated its activity against SARS-CoV-2. Subsequent clinical studies showed the efficacy of remdesivir in shortening the time to recovery. Aim. To evaluate the effect of the carriage of polymorphic alleles of the CES1 gene (A > C, rs2244613) on the safety profile of remdesivir therapy. Materials and methods. A total of 154 patients hospitalized with coronavirus infection were included in the study. All patients received remdesivir as etiotropic therapy in the standard regimen: 200 mg on the first day followed by 100 mg daily for 5-10 days. In the course of observations, clinical and laboratory signs of adverse events were reported. Venous blood samples were collected from each patient for pharmacogenetic studies. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: вata were analysed by using IBM SPSS Statistics, Version 23.0. Results. There were no significant associations of carriage of various CES1 variants with the frequency of adverse reactions (bradycardia, nausea, vomiting) and laboratory markers of adverse events (ALT, AST, creatinine levels). Conclusion. In our study, no association was found between the carriage of CES1 gene polymorphisms and the safety parameters of remdesivir in hospitalized patients with COVID-19. Further research into the possibilities of personalizing COVID-19 therapy through pharmacogenetic testing is needed. © 2022, Remedium Group Ltd. All rights reserved.

Evaluation of the association of CES1 (rs2244613) polymorphisms with the safety of remdesivir in hospitalized patients with COVID-19

Introduction. An outbreak of novel COVID-19 infection has become a real challenge for the entire human society, and first of all for the healthcare services. The development of new drugs is a complex and lengthy process. At the beginning of the pandemic, it forced an intensive study of well-known drugs for the therapy. Remdesivir was first investigated as a potential treatment for Ebola virus. After beginning of the COVID-19 pandemic, in vitro evaluations demonstrated its activity against SARS-CoV-2. Subsequent clinical studies showed the efficacy of remdesivir in shortening the time to recovery. Aim. To evaluate the effect of the carriage of polymorphic alleles of the CES1 gene (A > C, rs2244613) on the safety profile of remdesivir therapy. Materials and methods. A total of 154 patients hospitalized with coronavirus infection were included in the study. All patients received remdesivir as etiotropic therapy in the standard regimen: 200 mg on the first day followed by 100 mg daily for 5-10 days. In the course of observations, clinical and laboratory signs of adverse events were reported. Venous blood samples were collected from each patient for pharmacogenetic studies. Genotyping was performed using the real-time polymerase chain reaction technique. Statistical analysis: вata were analysed by using IBM SPSS Statistics, Version 23.0. Results. There were no significant associations of carriage of various CES1 variants with the frequency of adverse reactions (bradycardia, nausea, vomiting) and laboratory markers of adverse events (ALT, AST, creatinine levels). Conclusion. In our study, no association was found between the carriage of CES1 gene polymorphisms and the safety parameters of remdesivir in hospitalized patients with COVID-19. Further research into the possibilities of personalizing COVID-19 therapy through pharmacogenetic testing is needed. © 2022, Remedium Group Ltd. All rights reserved.

CYP2D6 phenotypes and opioid metabolism: the path to personalized analgesia.

INTRODUCTION: Opioids play a fundamental role in chronic pain, especially considering when 1 of 5 Europeans adults, even more in older females, suffer from it. However, half of them do not reach an adequate pain relief. Could pharmacogenomics help to choose the most appropriate analgesic drug? AREAS COVERED: The objective of the present narrative review was to assess the influence of cytochrome P450 2D6 (CYP2D6) phenotypes on pain relief, analgesic tolerability, and potential opioid misuse. Until December 2021, a literature search was conducted through the MEDLINE, PubMed database, including papers from the last 10 years. CYP2D6 plays a major role in metabolism that directly impacts on opioid (tramadol, codeine, or oxycodone) concentration with differences between sexes, with a female trend toward poorer pain control. In fact, CYP2D6 gene variants are the most actionable to be translated into clinical practice according to regulatory drug agencies and international guidelines. EXPERT OPINION: CYP2D6 genotype can influence opioids' pharmacokinetics, effectiveness, side effects, and average opioid dose. This knowledge needs to be incorporated in pain management. Environmental factors, psychological together with genetic factors, under a sex perspective, must be considered when you are selecting the most personalized pain therapy for your patients.

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in Subjects with Pulmonary Arterial Hypertension (ADVANCE OUTCOMES)

RATIONALE: Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right ventricular failure and premature death. The functional limitation and survival of patients with PAH remains unsatisfactory. Ralinepag, an orally available, potent, and selective, nonprostanoid, prostacyclin receptor agonist, is a new chemical entity in development to treat PAH. METHODS: The ADVANCE OUTCOMES (NCT03626688) study is a randomized, double-blind, placebocontrolled, event-driven study evaluating the efficacy and safety of ralinepag in subjects with PAH. In this event-driven, Phase 3 study, approximately 700 subjects with PAH treated with standard of care are randomly assigned (1:1) to receive ralinepag or placebo. Dosing is individualized and titrated based on tolerability and clinical response. The primary objective is to assess the effect of ralinepag on the time to first adjudicated clinical worsening event;a composite endpoint including death, hospitalization due to worsening of PAH, initiation of inhaled or infused prostacyclins, disease progression, or unsatisfactory long-term response. Additional secondary assessments during the study include changes from Baseline to Week 28 in N-terminal pro-brain natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), WHO/New York Heart Association (NYHA) Functional Class, and health-related quality of life measures. Exploratory assessments will evaluate biomarkers and pharmacogenetics. Subject safety is evaluated by capturing adverse events, hospitalizations, clinical laboratory, and ECG parameters. Subjects who experience a clinical worsening event or are participating at study closure are eligible to enter an open-label extension study (ROR-PH-303 [NCT03683186]). Long-term survival will be followed for all subjects until study closure. RESULTS: Enrollment is ongoing at approximately 200 sites in 33 countries following implementation of risk mitigation steps related to the Covid-19 pandemic. Enrollment will continue until 228 adjudicated clinical worsening events have occurred. The interim assessment includes 281 subjects randomized in 29 different countries;97% of participants have completed 28 weeks of treatment. The majority of subjects were female (79.4%) with a median age of 48.0 years, were receiving dual background therapy (82.9%), and were classified as Functional Class II (59.3%). Overall, 48 clinical worsening events have been reported at the time of the interim assessment. Of these, 34 subjects elected to continue treatment in the open-label extension study. An independent Data Monitoring Committee reviewed safety data after 50, 100, and 250 subjects were randomized and recommended study continuation without modification. CONCLUSIONS: ADVANCE OUTCOMES will assess whether ralinepag can improve function, delay disease progression, and prolong survival in subjects with PAH.

Will the Use of Pharmacogenetics Improve Treatment Efficiency in COVID-19?

The COVID-19 pandemic is associated with a global health crisis and the greatest challenge for scientists and doctors. The virus causes severe acute respiratory syndrome with an outcome that is fatal in more vulnerable populations. Due to the need to find an efficient treatment in a short time, there were several drugs that were repurposed or repositioned for COVID-19. There are many types of available COVID-19 therapies, including antiviral agents (remdesivir, lopinavir/ritonavir, oseltamivir), antibiotics (azithromycin), antiparasitics (chloroquine, hydroxychloroquine, ivermectin), and corticosteroids (dexamethasone). A combination of antivirals with various mechanisms of action may be more efficient. However, the use of some of these medicines can be related to the occurrence of adverse effects. Some promising drug candidates have been found to be ineffective in clinical trials. The knowledge of pharmacogenetic issues, which translate into variability in drug conversion from prodrug into drug, metabolism as well as transport, could help to predict treatment efficiency and the occurrence of adverse effects in patients. However, many drugs used for the treatment of COVID-19 have not undergone pharmacogenetic studies, perhaps as a result of the lack of time.

mRNA Vaccine: Determinants of Clinical Efficacy, and Optimization of Pharmacological Effects

The messenger ribonucleic acid (mRNA) vaccine has proven to be beneficial in containing the severe acute respiratory syndrome coronavirus. However, some school thought that it is not as effective as proposed, even though many others attest to its efficacy. The study employed scoping review on online journal and book publications to reveal the pharmacokinetics and pharmacodynamics of the mRNA vaccine. In this work, we have discussed the mechanism of action of the self-amplified messenger ribonucleic acid vaccines, the determinants of the clinical efficacy, and the possible reasons behind the varying efficacies that different populations may experience. We provided possible ways to tackle this challenge. In providing these solutions, we discussed pharmacogenetics viz-a-viz epigenetics. The study also used figures to elaborate on the factors that determine the clinical efficacy of mRNA vaccines. We are confident that caregivers and public health officials in the tropics would find the information interesting and invaluable.

Pharmacists closing health disparity gaps through pharmacogenomics

As the health care community recognizes the need to address health disparities, practitioners are working diligently to promote health equity. It is each of our responsibilities to identify and work to overcome barriers to equitable health care that our patients experience. Many factors contribute to health care disparities across the country, and because of this, health care providers must employ different strategies to resolve gaps in equity. Precision medicine and its constituent element of pharmacogenomics offer a unique opportunity to lead the way in serving patients as individuals with varying needs. Pharmacogenomics can be used as a solution for breaking down barriers including the lack of diversity in research, access for rural or underserved geographical locations, overcoming economic factors, improving education, and increasing technological portability. In this article, we review how clinical pharmacists using pharmacogenomics can play a key role in identifying and overcoming some of these barriers that lead to health care disparities.

Neurofibromatosis: New Clinical Challenges in the Era of COVID-19.

Rare diseases constitute a wide range of disorders thus defined for their low prevalence. However, taken together, rare diseases impact a considerable percentage of the world population, thus representing a public healthcare problem. In particular, neurofibromatoses are autosomal-dominant genetic disorders that include type 1 neurofibromatosis (NF1), type 2 neurofibromatosis (NF2) and schwannomatosis. Each of the three types is a genetically distinct disease with an unpredictable clinical course and for which there is still no resolutive cure. Therefore, a personalized therapeutic approach directed at improving the symptomatology as well as the search for new pharmacological strategies for the management of neurofibromatosis represents a priority for positive outcomes for affected patients. The coronavirus disease 2019 (COVID-19) pandemic has severely affected health systems around the world, impacting the provision of medical care and modifying clinical surveillance along with scientific research procedures. COVID-19 significantly worsened exchanges between healthcare personnel and neurofibromatosis patients, precluding continuous clinical monitoring in specialized clinic centers. In this new scenario, our article presents, for the first time, a comprehensive literature review on the clinical challenges for neurofibromatosis clinical care and research during the COVID-19 pandemic health emergency. The review was performed through PubMed (Medline) and Google Scholar databases until December 2021.

Three program enhancements to advance population genetic screening in a community health system during 2020

Introduction: Over the last five years, our health system has focusedon integrating genetics into primary care, as a part of routine medicalcare. Building on our previous genetic initiative implementationresearch findings from key stakeholders in primary care, severalcritical areas were identified for improvement: an enhanced clinicianeducation and feedback mechanism and a more robust integration ofgenetics in the electronic health record (EHR). To address these areas,we implemented three key enhancements: the Genomic Ambassadorprogram, Genomic Indicator, and Care Pathway.Population Genetic Testing Program Evolution: After the conclusionof our pilot population genetic testing program, DNA-10 K, theprimary care genetics program shifted to merging our two previousprimary care projects, the Genetic Wellness Assessment (GWA) andDNA-10 K. The GWA is a targeted family history tool. Patients seen fortheir annual physical exam at one of 14 primary care sites (InternalMedicine, Family Medicine, OB/GYN) qualified for this program. Thesepatients complete the GWA and are then offered a 74 gene nextgenerationsequencing panel assessing pharmacogenetics, hereditarycancer, and cardiovascular risk, as well as a low-pass whole genomeassay to assess “fun facts and traits” (e.g., ancestry, cilantropreference). The test is the same panel used in DNA-10 K and had anout-of-pocket cost of $175. The merged program started on January 20,2020. COVID-19 offered an opportunity to challenge our implementationand determine if we have been able to sustainably embedgenetics in primary care in the face of newchallenges encountered byour primary care physicians.Enhancements: The Genomic Ambassador program is an educationand feedback forum consisting of 8 volunteer primary care clinicians.This group met once a month, and the clinicians received a stipend fortheir efforts. The meetings had alternating focuses between geneticseducation and program feedback. The genetic education sessionsincluded basic scientific information, clinical cases, and practicalinformation about clinical decision support tools in our EHR. Thefeedback sessions were used to hear directly from the clinicians whatwas working and was not working, and solicit solutions for theproblems identified. These sessions were especially helpful in understandingthe additional pressure on the practices due to COVID-19.After the ambassadors completed eight months of the program, theywere trained to become peer-to-peer educators in their practices. Genomic Indicators and Care Pathways are tools available in the EPICEHR. Genomic indicators are structured as discrete groupings such asBRCA1 pathogenic variant. They are automatically assigned to apatient when their genetic results have resulted in the EHR. TheGenomics indicators have been linked to a short summary andexternal links to provide clinicians with real-time genetic educationalopportunities. Additionally, genomic indicators are used to assign acare pathway to patients. Care pathways are a structured tool that laysout the recommended path a patient takes for screening after apathogenic, or likely pathogenic, variant has been identified. To date,we have only developed a care pathway for breast cancer screening. Itis currently being used to track how well patients adhere torecommendations and identify areas of improvement. Preliminarywork has begun on a care pathway for familial hypercholesterolemia.These enhancements are awork-in-progress and will need continuousevaluation and improvement to increase our patient population’sunderstanding, access, and use of genomic testing and follow-upservices.Conclusion: As a course of regular business, we reviewed ourutilization metrics for 2020, there were 130,364 patients whoqualified for the merged program from 1/20/2020 to 12/31/2020.Weekly completion rates for the GWA component ranged from 39.9%to 54.5%, with a mean of 46.8%, similar to previous versions of GWA.The weekly totals for patients completing testing ranged from 11 to113, with a mean of 50. At the end of 2020, through this program andt e DNA-10 K program, 12,350 patients had completed testing withtheir results integrated into the EHR. We believe this data highlightsthe progress made in making genetics a routine part of our healthsystem’s primary care.The Genomic Ambassador program, Genomic Indicator, and CarePathwaywere critical enhancements to the current program and likelycontributed to its ability to continue through COVID-19. Theseadditions provided an education mechanism, a feedback forum, andmade our EHR integration more robust. These types of programmaticsolutions will continue to be sought and evaluated in our healthsystem and may be key to other successful genomic testingimplementations.

Pharmacogenetics and Precision Medicine Approaches for the Improvement of COVID-19 Therapies.

Many drugs are being administered to tackle coronavirus disease 2019 (COVID-19) pandemic situations without establishing clinical effectiveness or tailoring safety. A repurposing strategy might be more effective and successful if pharmacogenetic interventions are being considered in future clinical studies/trials. Although it is very unlikely that there are almost no pharmacogenetic data for COVID-19 drugs, however, from inferring the pharmacokinetic (PK)/pharmacodynamic(PD) properties and some pharmacogenetic evidence in other diseases/clinical conditions, it is highly likely that pharmacogenetic associations are also feasible in at least some COVID-19 drugs. We strongly mandate to undertake a pharmacogenetic assessment for at least these drug-gene pairs (atazanavir-UGT1A1, ABCB1, SLCO1B1, APOA5; efavirenz-CYP2B6; nevirapine-HLA, CYP2B6, ABCB1; lopinavir-SLCO1B3, ABCC2; ribavirin-SLC28A2; tocilizumab-FCGR3A; ivermectin-ABCB1; oseltamivir-CES1, ABCB1; clopidogrel-CYP2C19, ABCB1, warfarin-CYP2C9, VKORC1; non-steroidal anti-inflammatory drugs (NSAIDs)-CYP2C9) in COVID-19 patients for advancing precision medicine. Molecular docking and computational studies are promising to achieve new therapeutics against SARS-CoV-2 infection. The current situation in the discovery of anti-SARS-CoV-2 agents at four important targets from in silico studies has been described and summarized in this review. Although natural occurring compounds from different herbs against SARS-CoV-2 infection are favorable, however, accurate experimental investigation of these compounds is warranted to provide insightful information. Moreover, clinical considerations of drug-drug interactions (DDIs) and drug-herb interactions (DHIs) of the existing repurposed drugs along with pharmacogenetic (e.g., efavirenz and CYP2B6) and herbogenetic (e.g., andrographolide and CYP2C9) interventions, collectively called multifactorial drug-gene interactions (DGIs), may further accelerate the development of precision COVID-19 therapies in the real-world clinical settings.

The Contribution of Pharmacogenetic Drug Interactions to 90-Day Hospital Readmissions: Preliminary Results from a Real-World Healthcare System.

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines exist for many medications commonly prescribed prior to hospital discharge, yet there are limited data regarding the contribution of gene-x-drug interactions to hospital readmissions. The present study evaluated the relationship between prescription of CPIC medications prescribed within 30 days of hospital admission and 90-day hospital readmission from 2010 to 2020 in a study population (N = 10,104) who underwent sequencing with a 14-gene pharmacogenetic panel. The presence of at least one pharmacogenetic indicator for a medication prescribed within 30 days of hospital admission was considered a gene-x-drug interaction. Multivariable logistic regression analyzed the association between one or more gene-x-drug interactions with 90-day readmission. There were 2211/2354 (93.9%) admitted patients who were prescribed at least one CPIC medication. Univariate analyses indicated that the presence of at least one identified gene-x-drug interaction increased the risk of 90-day readmission by more than 40% (OR = 1.42, 95% confidence interval (CI) 1.09-1.84) (p = 0.01). A multivariable model adjusting for age, race, sex, employment status, body mass index, and medical conditions slightly attenuated the effect (OR = 1.32, 95% CI 1.02-1.73) (p = 0.04). Our results suggest that the presence of one or more CPIC gene-x-drug interactions increases the risk of 90-day hospital readmission, even after adjustment for demographic and clinical risk factors.