Adverse Cardiovascular Effects of Anti-COVID-19 Drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or COVID-19 infection is the cause of the ongoing global pandemic. Mortality from COVID-19 infection is particularly high in patients with cardiovascular diseases. In addition, COVID-19 patients with preexisting cardiovascular comorbidities have a higher risk of death. Main cardiovascular complications of COVID-19 are myocardial infarction, myocarditis, acute myocardial injury, arrhythmias, heart failure, stroke, and venous thromboembolism. Therapeutic interventions in terms of drugs for COVID-19 have many cardiac adverse effects. Here, we review the relative therapeutic efficacy and adverse effects of anti-COVID-19 drugs.

Safety assessment of drug combinations used in COVID-19 treatment: in silico toxicogenomic data-mining approach.

Improvement of COVID-19 clinical condition was seen in studies where combination of antiretroviral drugs, lopinavir and ritonavir, as well as immunomodulant antimalaric, chloroquine/hydroxychloroquine together with the macrolide-type antibiotic, azithromycin, was used for patient's treatment. Although these drugs are "old", their pharmacological and toxicological profile in SARS-CoV-2 - infected patients are still unknown. Thus, by using in silico toxicogenomic data-mining approach, we aimed to assess both risks and benefits of the COVID-19 treatment with the most promising candidate drugs combinations: lopinavir/ritonavir and chloroquine/hydroxychloroquine + azithromycin. The Comparative Toxicogenomics Database (CTD; http://CTD.mdibl.org), Cytoscape software (https://cytoscape.org) and ToppGene Suite portal (https://toppgene.cchmc.org) served as a foundation in our research. Our results have demonstrated that lopinavir/ritonavir increased the expression of the genes involved in immune response and lipid metabolism (IL6, ICAM1, CCL2, TNF, APOA1, etc.). Chloroquine/hydroxychloroquine + azithromycin interacted with 6 genes (CCL2, CTSB, CXCL8, IL1B, IL6 and TNF), whereas chloroquine and azithromycin affected two additional genes (BCL2L1 and CYP3A4), which might be a reason behind a greater number of consequential diseases. In contrast to lopinavir/ritonavir, chloroquine/hydroxychloroquine + azithromycin downregulated the expression of TNF and IL6. As expected, inflammation, cardiotoxicity, and dyslipidaemias were revealed as the main risks of lopinavir/ritonavir treatment, while chloroquine/hydroxychloroquine + azithromycin therapy was additionally linked to gastrointestinal and skin diseases. According to our results, these drug combinations should be administrated with caution to patients suffering from cardiovascular problems, autoimmune diseases, or acquired and hereditary lipid disorders.