Background and objective Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and subsequent infectivity are mediated by androgens and the androgen receptors through the regulation of transmembrane protease, serine 2 (TMPRSS2). Androgenetic alopecia (AGA) predisposes males to severe coronavirus disease 2019 (COVID-19) disease, while the use of 5-alpha-reductase inhibitors (5ARis) and androgen receptor antagonists reduce COVID-19 disease severity. In this study, we aimed to determine the potential benefit of dutasteride, a commonly used broad and potent 5ARi, as a treatment for COVID-19. Design, setting, and participants The study was conducted at outpatient clinics. Subjects presented to the clinics with a positive reverse transcription-polymerase chain reaction (RT-PCR) test taken within 24 hours of recruitment. All subjects presented with mild to moderate symptoms. Interventions Subjects were given either dutasteride 0.5 mg/day or placebo for 30 days or until full COVID-19 remission. All subjects received standard therapy with nitazoxanide 500 mg twice a day for six days and azithromycin 500 mg/day for five days. Main outcome(s) and measure(s) The main outcome(s) and measure(s) were as follows: time to remission, oxygen saturation (%), positivity rates of RT-PCR-SARS-CoV-2, and biochemical analysis [ultrasensitive C-reactive protein (usCRP), D-dimer, lactate, lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR), ultrasensitive troponin, and ferritin]. Results Subjects taking dutasteride (n=43) demonstrated reduced fatigue, anosmia, and overall disease duration compared to subjects taking a placebo (n=44) (p<.0001 for all). Compared to the placebo group, on Day seven, subjects taking dutasteride had a higher virologic remission rate (64.3% versus 11.8%; p=.0094), higher clinical recovery rate (84.7% versus 57.5%; p=.03), higher mean [standard deviation: SD] oxygen saturation (97.0% [1.4%] versus 95.7% [2.0%]; p=.02), lower median [Interquartile range: IQR] usCRP (0.34 mg/L [0.23 mg/L-0.66 mg/L] versus 1.47 mg/L [0.70 mg/L-3.37 mg/L]; p<.0001), lower median [IQR] lactate (2.01 mmol/L [1.12 mmol/L-2.43 mmol/L] versus 2.66 mmol/L [2.05 mmol/L-3.55 mmol/L]; p=.0049), lower median [IQR] ESR (5.0 mm/1h [3.0 mm/1h-11.0 mm/1h] versus 14.0 mm/1h [7.25 mm/1h-18.5 mm/1h]; p=.0007), lower median [IQR] LDH (165 U/L [144 U/L-198 U/L] versus 210 U/L [179 U/L-249 U/L]; p=.0013) and lower median [IQR] troponin levels (0.005 ng/mL [0.003 ng/mL-0.009 ng/mL] versus 0.007 ng/mL [0.006 ng/mL-0.010 ng/mL]; p=.048). Conclusions and relevance The findings from this study suggest that in males with mild COVID-19 symptoms undergoing early therapy with nitazoxanide and azithromycin, treatment with dutasteride reduces viral shedding and inflammatory markers compared to males treated with a placebo.
【저자키워드】 COVID-19, SARS-CoV-2, Azithromycin, nitazoxanide, dutasteride, 【초록키워드】 Treatment, coronavirus, therapy, fatigue, viral shedding, LDH, C-reactive protein, D-dimer, protease, Symptoms, Anosmia, clinics, clinical recovery, oxygen saturation, male, Mild, Placebo, ESR, Inflammatory marker, receptor, recruitment, inhibitor, disease, moderate, Lactate, Analysis, androgen, Standard therapy, erythrocyte sedimentation rate, acute respiratory syndrome, Regulation, biochemical, severe coronavirus disease, subject, cell entry, COVID-19 disease severity, participant, transmembrane, positive, antagonist, serine 2, FIVE, benefit, Seven, Result, subsequent, Day, conducted, reduced, median, treated, determine, were given, demonstrated, reduce, 24 hour, AGA, mild COVID-19 symptom, the placebo group, treatment for COVID-19, troponin level, 【제목키워드】 shedding, antiandrogen,