ABSTRACT
BACKGROUND: P.1 lineage (Gamma) was first described in the State of Amazonas, northern Brazil, in the end of 2020, and has emerged as a very important variant of concern (VOC) of SARS-CoV-2 worldwide. P.1 has been linked to increased infectivity, higher mortality, and immune evasion, leading to reinfections and potentially reduced efficacy of vaccines and neutralizing antibodies. METHODS: The samples of 276 patients from the State of Amazonas were sent to a central referral laboratory for sequencing by gold standard techniques, through Illumina MiSeq platform. Both global and regional phylogenetic analyses of the successfully sequenced genomes were conducted through maximum likelihood method. Multiple alignments were obtained including previously obtained unique human SARS-CoV-2 sequences. The evolutionary histories of spike and non-structural proteins from ORF1a of northern genomes were described and their molecular evolution was analyzed for detection of positive (FUBAR, FEL, and MEME) and negative (FEL and SLAC) selective pressures. To further evaluate the possible pathways of evolution leading to the emergence of P.1, we performed specific analysis for copy-choice recombination events. A global phylogenomic analysis with subsampled P.1 and B.1.1.28 genomes was applied to evaluate the relationship among samples. RESULTS: Forty-four samples from the State of Amazonas were successfully sequenced and confirmed as P.1 (Gamma) lineage. In addition to previously described P.1 characteristic mutations, we find evidence of continuous diversification of SARS-CoV-2, as rare and previously unseen P.1 mutations were detected in spike and non-structural protein from ORF1a. No evidence of recombination was found. Several sites were demonstrated to be under positive and negative selection, with various mutations identified mostly in P.1 lineage. According to the Pango assignment, phylogenomic analyses indicate all samples as belonging to the P.1 lineage. CONCLUSION: P.1 has shown continuous evolution after its emergence. The lack of clear evidence for recombination and the positive selection demonstrated for several sites suggest that this lineage emergence resulted mainly from strong evolutionary forces and progressive accumulation of a favorable signature set of mutations.
ABSTRACT
A severe case of COVID-19 was observed in an otherwise healthy 28-year-old man who had taken oxandrolone 40 mg/day as an anabolic steroid. The patient had been taking oxandrolone for enhanced bodybuilding 30 days prior to presenting to an outpatient clinic with COVID-19 symptoms. The patient reported that his symptoms have rapidly worsened over the course of 4 days prior to presenting at the clinic. As part of an experimental antiandrogen treatment for hyperandrogenic men suffering from COVID-19, he was administered a single 600 mg dose of the novel antiandrogen proxalutamide. Twenty-four hours after administration of this dose, marked improvement of symptoms and markers of disease severity were observed. To our knowledge, this is the first case that potentially links anabolic steroid use to COVID-19 disease severity.
Subject(s)
Anabolic Agents/adverse effects , Androgen Antagonists/administration & dosage , COVID-19 Drug Treatment , Oxandrolone/adverse effects , Oxazoles/administration & dosage , Thiohydantoins/administration & dosage , Adult , Anabolic Agents/administration & dosage , Disease Progression , Humans , Male , Oxandrolone/administration & dosage , Performance-Enhancing Substances/adverse effects , SARS-CoV-2 , Severity of Illness IndexABSTRACT
Acredita-se que a dermatite seborreica do couro cabeludo, ou caspa, piore em gravidade durante o inverno, quando ocorre o nascer do sol tardio e menos luz do dia. Neste estudo, investigamos as tendências no interesse do mecanismo de pesquisa pelo termo "caspa", visto que se relacionam com as mudanças na luz do dia, nascer do sol e sazonalidade. Analisamos o interesse de pesquisa em vários países de latitudes variáveis em um período de cinco anos e exploramos o efeito do horário de verão sobre o interesse por doenças em duas cidades dos Estados Unidos. Discutimos nossas descobertas no contexto de mudanças hormonais e cuidados com a pele/comportamento
Scalp seborrheic dermatitis, or dandruff, is thought to worsen during the winter when there is later sunrise and less daylight. This study investigates trends in search engine interest for the term "dandruff" as they relate to changes in daylight, sunrise, and seasonality. We investigated the search interest in several countries of varying latitudes over a five-year period, and we explore the effect of daylight saving time on disease interest within two cities in the United States. We discuss our findings in the context of hormonal changes and skincare/behavior