An open-label prospective observational study of antiandrogen and non-antiandrogen early pharmacological approaches in females with mild-to-moderate COVID-19. The Pre-AndroCoV Female Trial
MD, MSc Flavio A Cadegiani, Andy Goren, Carlos G Wambier, John Mccoy
doi:10.1101/2020.10.05.20206870
Background: While COVID-19 remains largely unclear and mortality continues to raise, early effective approaches prior to complications lack, as well as researches for characterization and therapeutical potential options in actual early COVID-19. Although females seem to be less affected than females, hyperandrogenic (HA) phenotype, like polycystic ovary syndrome (PCOS), idiopathic hirsutism, congenital adrenal hyperplasia (CAH) female androgenetic alopecia (AGA), or idiopathic HA may be at higher risk due to its inherent enhanced androgenic activity. The present study aimed to evaluate the effects of any early pharmacological approach to females diagnosed with COVID-19 .
References
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'abstract': '<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>While '
'COVID-19 remains largely unclear and mortality continues to raise, early effective approaches '
'prior to complications lack, as well as researches for characterization and therapeutical '
'potential options in actual early COVID-19. Although females seem to be less affected than '
'females, hyperandrogenic (HA) phenotype, like polycystic ovary syndrome (PCOS), idiopathic '
'hirsutism, congenital adrenal hyperplasia (CAH) female androgenetic alopecia (AGA), or '
'idiopathic HA may be at higher risk due to its inherent enhanced androgenic activity. The '
'present study aimed to evaluate the effects of any early pharmacological approach to females '
'diagnosed with COVID-19 before seven days of symptoms, as well as investigate whether HA is '
'an additional risk factor in this '
'population.</jats:p></jats:sec><jats:sec><jats:title>Materials and '
'methods</jats:title><jats:p>Females with symptoms for less than seven days confirmed for '
'COVID-19 through positive real-time polymerase chain reaction (rtPCR-SARS-CoV-2) were '
'classified and divided as non-HA, HA, and HA using spironolactone (HA-spiro) groups. Patients '
'were questioned for baseline characteristics, 23 different diseases, 44 drug classes and '
'vaccines, 28 different symptoms, and eight different parameters to measure COVID-19 related '
'clinical outcomes. Treatment was then provided, including azithromycin 500mg/day for five '
'days in all cases, associated with hydroxychloroquine 400mg/day for five days, nitazoxanide '
'500mg twice a day for six days, or ivermectin 0.2mg/kg/day por three days, and optionally '
'spironolactone 100mg twice a day until cure. Patients were assessed for COVID-19 clinical '
'course, clinical and viral duration, and disease '
'progression.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, '
'270 females were enrolled, including 195, 67, and eight in non-HA, HA, and HA-spiro groups, '
'respectively. Prevailing symptoms were anosmia (71.1%), ageusia (67.0%), headache (48.1%), '
'myalgia (37.4%), dry cough (36.3%), nasal congestion or rhinorrhea (34.1%), fatigue (33.3%), '
'weakness (29.5%), hyporexia (27.8%), thoracic pain (24.8%), diarrhea (24.1%) and dizziness '
'(21.5%). Earliest symptoms (days) were dizziness (<jats:italic>1</jats:italic>.<jats:italic>0 '
'± 0</jats:italic>.<jats:italic>2 day), abdominal pain</jats:italic> '
'(<jats:italic>1</jats:italic>.<jats:italic>1 ± 0</jats:italic>.<jats:italic>3);</jats:italic> '
'conjunctival hyperemia (<jats:italic>1</jats:italic>.<jats:italic>1 ± '
'0</jats:italic>.<jats:italic>5)</jats:italic>, nasal congestion or rhinorrhea '
'(<jats:italic>1</jats:italic>.<jats:italic>2 ± 0</jats:italic>.<jats:italic>5)</jats:italic>, '
'headache (<jats:italic>1</jats:italic>.<jats:italic>2 ± 0</jats:italic>.<jats:italic>5), dry '
'cough</jats:italic> (<jats:italic>1</jats:italic>.<jats:italic>2 ± '
'0</jats:italic>.<jats:italic>5)</jats:italic>, myalgia '
'(<jats:italic>1</jats:italic>.<jats:italic>2 ± 0</jats:italic>.<jats:italic>4)</jats:italic>, '
'nauseas (<jats:italic>1</jats:italic>.<jats:italic>3 ± '
'0</jats:italic>.<jats:italic>5)</jats:italic> and weakness '
'(<jats:italic>1</jats:italic>.<jats:italic>3 ± 0</jats:italic>.<jats:italic>5)</jats:italic>. '
'Time-to-treat, positive rtPCR, and duration of symptoms with and without anosmia and ageusia '
'were significantly lower in HA-spiro than non-HA, HA, and overall non-users. Time-to-treat '
'was similar while all duration of symptoms and positive rtPCR-SARS-CoV-2 were significantly '
'shorter in non-HA than HA. Spironolactone users were more likely to be asymptomatic than '
'non-users during COVID-19. Fewer non-HA than HA females were affected by anosmia, ageusia, '
'dry cough, fatigue, weakness and hyporexia. Ageusia, weakness and myalgia lasted shorter in '
'non-HA than HA. None of the patients needed hospitalization or any other COVID-19 '
'complication.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>A '
'sensitive, early detection of COVID-19 followed by a pharmaceutical approach with different '
'drug combinations yielded irrefutable differences compared to sex-, age-, body mass index '
'(BMI)-, and disease-matched non-treated controls in terms of clinical outcomes, ethically '
'disallowing placebo-control randomized clinical trials in the early stage of COVID-19 due to '
'the marked improvements. HA females presented more severe and prolonged clinical '
'manifestations, although none progressed to worse outcomes. Spironolactone mitigated the '
'additional risks due to HA.</jats:p></jats:sec>',
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