Abstract
Drug-drug interactions (DDI) potentially occurring between medications used in the course of COVID-19 infection and medications prescribed for the management of underlying comorbidities may cause adverse drug reactions (ADRs) contributing to worsening of the clinical outcome in affected patients. First, we conducted a meta-analysis to determine comorbidities observed in the course of COVID-19 disease associated with an increased risk of worsened clinical outcome from 24 published studies. In addition, the potential risk of DDI between medications used in the course of COVID-19 treatment in these studies and those for the management of observed comorbidities was evaluated for possible worsening of the clinical outcome. Our meta-analysis revealed an implication cardiometabolic syndrome (e.g. cardiovascular disease, cerebrovascular disease, hypertension, and diabetes), chronic kidney disease and chronic obstructive pulmonary disease as main co-morbidities associated with worsen the clinical outcomes including mortality (risk difference RD 0.12, 95 %-CI 0.05−0.19, p = 0.001), admission to ICU (RD 0.10, 95 %-CI 0.04−0.16, p = 0.001) and severe infection (RD 0.05, 95 %-CI 0.01−0.09, p = 0.01) in COVID-19 patients. Potential DDI on pharmacokinetic level were identified between the antiviral agents atazanavir and lopinavir/ritonavir and some drugs, used in the treatment of cardiovascular diseases such as antiarrhythmics and anti-coagulants possibly affecting the clinical outcome including cardiac injury or arrest because of QTc-time prolongation or bleeding. Concluding, DDI occurring in the course of anti-Covid-19 treatment and co-morbidities could lead to ADRs, increasing the risk of hospitalization, prolonged time to recovery or death on extreme cases. COVID-19 patients with cardiometabolic diseases, chronic kidney disease and chronic obstructive pulmonary disease should be subjected to particular carefully clinical monitoring of adverse events with a possibility of dose adjustment when necessary.
【저자키워드】 COVID-19, SARS-CoV-2, Comorbidity, drug-drug interaction, Side-effect, 【초록키워드】 Treatment, Meta-analysis, Severe infection, Mortality, Hospitalization, drugs, risk, cardiovascular disease, Chronic kidney disease, diabetes, hypertension, ICU, COVID-19 disease, Clinical outcome, COVID-19 infection, management, adverse event, bleeding, death, co-morbidity, Time to recovery, medication, antiviral agent, Admission, patients, COVID-19 patients, pulmonary disease, ADRS, cardiometabolic, Adverse drug reaction, pharmacokinetic, Interaction, dose, Injury, Cerebrovascular disease, COVID-19 patient, increased risk, worsening, potential risk, syndrome, cardiometabolic diseases, clinical monitoring, extreme, Course, affected, addition, evaluated, conducted, determine, contributing to, affecting, Potential, chronic obstructive, worsened,