isotretinoin in treatment of covid-19

Conditions: COVID-19

Summary: contributors: lamia elgarhy, sabah el-gaeish 1, eman hamed 2 , wagdy fathy2 department of dermatology, department of pharmacology1 , faculty of medicine, tanta university, department of chest, faculty of medicine, suez canal university2. abstract: the covid-19 pandemic caused by sars-cov-2 has infected over 2,000,000 people causing over 150,000 deaths. a key host cellular protein required for the virus entry is angiotensin-converting enzyme 2 (ace2) whose expression has been demonstrated in many tissues including alveolar epithelial type ii cells in lungs, oral mucosa and intestine, heart, kidney, endothelium and skin. ace2-expressing cells can act as home cells and are prone to sars-cov-2 infection as ace2 receptor facilitates cellular viral entry and replication. (1) fang et al. has suggested that patients with hypertension and diabetes mellitus may be at higher risk of sars-cov-2 infection, as these patients are often treated with ace inhibitors (aceis) or angiotensin ii type-i receptor blockers (arbs), which have been previously suggested to increase ace2 expression. (2) in another study by sinha et al who analyzed a publicly available connectivity map (cmap) dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules, isotretinoin was the strongest down-regulator of ace 2 receptors. on the other hand, they found 6 drugs in cmap that are currently being investigated in clinical trials for treating covid-19 (chloroquine, thalidomide, methylprednisolone, losartan, lopinavir and ritonavir, from clinicaltrials.gov), none of which was found to significantly alter ace2 expression (p\>0.1) (3) moreover, wu et al, demonstrated that isotretinoin is a potential papain like protease (plpro) inhibitors which is a protein encoded by sars-cov-2 genes and considered one of the proteins that should be targeted in covid-19 treatment by performing target-based virtual ligand screening. (4) in addition, isotretinoin was reported to increase cd4 counts and markedly decrease viremia in hiv positive patients suffering from acne vulgaris. (5) currently, a study is running to evaluate the effect of isotretinoin on immune activation among hiv-1 infected subjects with incomplete cd4+ t cell recovery. (6) from this point, we can suggest that patient taking isotretinoin therapy may be immune against sars-cov-2 and it can also have a therapeutic effect by prevention of further progression of the virus. several potential mechanisms of action of chloroquine/hydroxychloroquine against sars-cov-2 have been postulated and they are actually used in treatment regimens for covid-19.(7) it was reported that chloroquine increase the blood level of isotretinoin, so lower doses is required when combined. we assume to test the efficacy of isotretinoin in treatment of covid-19 versus combined therapy with the standard treatment of covid-19.

the study is a randomized interventional comparative phase iii trial. the duration of the trial for each subject is expected to be 3 months. the duration for each individual subject includes one-month study treatment and 3 months follow-up time. recruitment of subjects will start in april 2020. 150 adult male and female patients with positive covid-19 diagnosis and fulfilling the below outlined inclusion criteria will be enrolled into the study. trial population will consist of both genders. name of tested drug: isotretinoin. all consenting adult patients having confirmed covid-19 will be recruited and randomly and blindly allocated in a 1:1:1 ratio to the following arms: group (1): 50 patients will receive isotretinoin 0.5 mg/kg/day for one month or until viral clearance. group (2): 50 patients will receive standard therapy for covid-19 (paracetamol 500 mg /6h, hydroxychloroquine 500 mg/ 12h, oseltamivir 150 mg /12 h for 5 days, azithromycin 1 gm first day then 500 mg/day for 1st line or clarithromycin 500 mg/12 h for 7-14 days, ascorbic acid 500 mg/12 h and cyanocobalamin iv once daily plus lopinavir 400mg/ritonavir 100 mg caps 2 capsules twice daily in severe cases). group (3): 50 patients will receive standard therapy for covid-19 + isotretinoin 0.25 mg/kg/day for one month or until viral clearance. inclusion criteria: * clinical and laboratory diagnosis of covid-19. * age range 18-40 exclusion criteria: • have the following conditions: 1. hypercholesterolemia 2. hypertriglyceridemia 3. liver disease 4. renal disease 5. sjögren syndrome 6. pregnancy 7. lactation 8. depressive disorder 9. contraindications for hormonal contraception or intrauterine device.

Eligibility criteria:
inclusion criteria: * clinical and laboratory diagnosis of covid-19. * age range 18-40 exclusion criteria: 1. hypercholesterolemia 2. hypertriglyceridemia 3. liver disease 4. renal disease 5. sjögren syndrome 6. pregnancy 7. lactation 8. depressive disorder 9. contraindications for hormonal contraception or intrauterine device.

Keywords: isotretinoin covid-19