ABSTRACT
Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.
ABSTRACT
BACKGROUND: The cutaneous manifestations of COVID-19 may be useful disease markers and prognostic indicators. Recently, postinfectious telogen effluvium and trichodynia have also been reported. OBJECTIVE: To evaluate the presence of trichodynia and telogen effluvium in patients with COVID-19 and describe their characteristics in relation to the other signs and symptoms of the disease. METHODS: Patients with a history of COVID-19 presenting to the clinics of a group of hair experts because of telogen effluvium and/or scalp symptoms were questioned about their hair signs and symptoms in relation to the severity of COVID-19 and associated symptoms. RESULTS: Data from 128 patients were collected. Telogen effluvium was observed in 66.3% of the patients and trichodynia in 58.4%. Trichodynia was associated with telogen effluvium in 42.4% of the cases and anosmia and ageusia in 66.1% and 44.1% of the cases, respectively. In majority (62.5%) of the patients, the hair signs and symptoms started within the first month after COVID-19 diagnosis, and in 47.8% of the patients, these started after 12 weeks or more. LIMITATIONS: The recruitment of patients in specialized hair clinics, lack of a control group, and lack of recording of patient comorbidities. CONCLUSION: The severity of postviral telogen effluvium observed in patients with a history of COVID-19 infection may be influenced by COVID-19 severity. We identified early-onset (<4 weeks) and late-onset (>12 weeks) telogen effluvium.
Subject(s)
Alopecia Areata/complications , COVID-19/complications , Adult , Alopecia Areata/virology , COVID-19/immunology , Female , Humans , Interleukin-6/immunology , Male , Prognosis , SARS-CoV-2 , Time FactorsABSTRACT
Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into type II pneumocytes is dependent on a modification of viral spike proteins by transmembrane protease serine 2 (TMPRSS2) expressed on the surface of human cells. TMPRSS2 is regulated by the androgen receptor, hence, SARS-CoV-2 infectivity is indirectly dependent on androgenic status and phenotype. Previously, we have reported that men affected by androgenetic alopecia (AGA) are overrepresented in severe coronavirus disease 2019 (COVID-19). Additionally, we have reported that men taking antiandrogenic drugs, e.g., 5-alpha-reductase inhibitors (5ARis), are less likely to have severe COVID-19. Here we aimed to test whether the androgen receptor antagonist, Proxalutamide, would be a beneficial treatment for subjects with SARS-CoV-2 infection. Methods Male and female subjects were recruited to a double-blinded, randomized, prospective, investigational study of Proxalutamide for the treatment of COVID-19. Mild to moderate, non-hospitalized subjects, who were confirmed positive for SARS-CoV-2, were treated with either Proxalutamide 200 mg/day or placebo. Endpoints for the study were remission time (days) and the percentage of subjects confirmed negative for SARS-CoV-2 on Day 7 after treatment. A negative SARS-CoV-2 test was defined by concentration-time (Ct)>40 determined by real-time reverse transcription-polymerase chain reaction (rtPCR). Results Two-hundred thirty-six (2360 subjects were included in the study (108 female, 128 male); 171 were randomized to the Proxalutamide arm and 65 were in the placebo group. On Day 7, SARS-CoV-2 became non-detectable with rtPCR (cT>40) in 82% of the subjects in the Proxalutamide group versus 31% in the placebo group (p < 0.001). The average clinical remission time for patients treated with Proxalutamide was 4.2 ±5.4 days versus 21.8 ±13.0 days in the placebo arm (p < 0.001). Conclusion Proxalutamide significantly accelerated viral clearance on Day 7 in mild to moderate COVID-19 patients versus placebo. Further, the time to clinical remission was significantly reduced in patients treated with Proxalutamide versus placebo.
Subject(s)
COVID-19 Vaccines , COVID-19 , Alopecia , Animals , Gonadal Steroid Hormones , Humans , SARS-CoV-2 , T-Lymphocytes , TrichurisSubject(s)
Alopecia , Coronavirus Infections , Pandemics , Pneumonia, Viral , Alopecia/epidemiology , Betacoronavirus , COVID-19 , Epidemiologic Studies , Humans , SARS-CoV-2Subject(s)
COVID-19/complications , Exanthema/diagnosis , Mouth Diseases/diagnosis , Skin Diseases, Viral/diagnosis , Adult , Aged , COVID-19/diagnosis , COVID-19/virology , Diagnosis, Differential , Drug Eruptions/diagnosis , Exanthema/virology , Female , Humans , Male , Middle Aged , Mouth Diseases/pathology , Mouth Diseases/virology , Mouth Mucosa/pathology , Palate/pathology , SARS-CoV-2/isolation & purification , Skin Diseases, Viral/virologySubject(s)
Alopecia/epidemiology , Androgens/metabolism , Betacoronavirus/isolation & purification , Coronavirus Infections/diagnosis , Pneumonia, Viral/diagnosis , Severity of Illness Index , Adult , Aged , Aged, 80 and over , Alopecia/complications , Alopecia/metabolism , Androgen Antagonists/therapeutic use , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Prevalence , Receptors, Androgen/metabolism , SARS-CoV-2 , Spain/epidemiology , Young Adult , COVID-19 Drug TreatmentSubject(s)
Alopecia/genetics , Androgen Antagonists/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Genetic Variation , Pneumonia, Viral/drug therapy , Pneumonia, Viral/mortality , Prostatic Neoplasms/genetics , Racial Groups/genetics , Receptors, Androgen/genetics , COVID-19 , Humans , Male , PandemicsABSTRACT
A preliminary observation of high frequency of male pattern hair loss among admitted COVID-19 patients and suggest that androgen expression might be a clue to COVID-19 severity.