Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility

Chakladar, Jaideep; Shende, Neil; Li, Wei Tse; Rajasekaran, Mahadevan; Chang, Eric Y.; Ongkeko, Weg M.

doi:10.3390/ijms21103627

Cited by 41 publications

(65 citation statements)

References 24 publications

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“…Current smokers as compared with never smokers have significantly upregulated ACE2 expression in the lung and oral epithelium. [37][38][39] COPD also has been independently associated with increased ACE2 expression by approximately 50% compared with those without COPD. 38 Given that smoking and COPD are more prevalent among males, higher expression of ACE2 due to these risk factors may, in part, explain the worse outcomes of COVID-19 in males.…”

Section: Ace2 and Tmprss2: Sex Differences In Expression And Regulationmentioning

confidence: 99%

COVID-19 and Sex Differences

Vermunt

Abeykoon

et al. 2020

Mayo Clinic Proceedings

245

127

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Men are consistently overrepresented in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and coronavirus disease 2019 (COVID-19) severe outcomes, including higher fatality rates. These differences are likely due to gender-specific behaviors, genetic and hormonal factors, and sex differences in biological pathways related to SARS-CoV-2 infection. Several social, behavioral, and comorbid factors are implicated in the generally worse outcomes in men compared with women. Underlying biological sex differences and their effects on COVID-19 outcomes, however, have received less attention. The present review summarizes the available literature regarding proposed molecular and cellular markers of COVID-19 infection, their associations with health outcomes, and any reported modification by sex. Biological sex differences characterized by such biomarkers exist within healthy populations and also differ with age-and sex-specific conditions, such as pregnancy and menopause. In the context of COVID-19, descriptive biomarker levels are often reported by sex, but data pertaining to the effect of patient sex on the relationship between biomarkers and COVID-19 disease severity/outcomes are scarce. Such biomarkers may offer plausible explanations for the worse COVID-19 outcomes seen in men. There is the need for larger studies with sex-specific reporting and robust analyses to elucidate how sex modifies cellular and molecular pathways associated with SARS-CoV-2. This will improve interpretation of biomarkers and clinical management of COVID-19 patients by facilitating a personalized medical approach to risk stratification, prevention, and treatment.

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Section: Ace2 and Tmprss2: Sex Differences In Expression And Regulationmentioning

confidence: 99%

COVID-19 and Sex Differences

Vermunt

Abeykoon

et al. 2020

Mayo Clinic Proceedings

245

127

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“…Também existe a discussão em torno de ações hormonais à predisposição à COVID-19. Chakladar et al (2020) relatam que fumar pode regular positivamente a expressão de ACE2 por meio da regulação positiva da via androgênica (Shiota et al, 2019), por meio dos genes reguladores da via central. Esses dados fornecem um modelo potencial para o aumento da suscetibilidade de pacientes fumantes ao COVID-19 e incentivam uma exploração adicional na regulação positiva de andrógenos e tabaco da ACE2 para entender as possíveis ramificações clínicas.…”

Section: Resultsunclassified

Reflexões sobre a associação entre o tabagismo e COVID – 19: revisão de literatura

Pessoa

Santos

Rodrigues³

et al. 2020

RSD

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A patogênese do COVID-19 é amplamente desconhecida, e os dados são limitados sobre as características clínicas dos pacientes e seus fatores prognósticos, presumindo -se que o tabagismo esteja possivelmente associado ao prognóstico adverso da doença. Este trabalho tem como objetivo descrever baseando-se na literatura científica a associação entre o consumo de tabaco e a progressão da COVID-19. Trata-se de uma revisão de literatura do tipo integrativa, e realizaram-se buscas na base de dados PUBMED e BIREME, utilizando os descritores “tobacco” and “COVID-19”, de artigos completos e gratuitos publicados no ano de 2020. A amostra final desta revisão foi constituída por 8 (oito) artigos científicos. As principais alterações relacionadas com a progressão da COVID-19 em indivíduos tabagistas nos estudos analisados foram: maior expressão do gene do receptor ACE2 em fumantes, contribuindo com a progressão dos sintomas, o aumento da resposta inflamatória em fumantes subcrônicos de cigarros eletrônicos, o enriquecimento da via androgênica e à regulação positiva específica dos genes reguladores da via central e a realização de campanhas de combate ao tabagismo. Enquanto os processos fisiopatológicos relacionados não forem totalmente elucidados, é importante reforçar as campanhas de manutenção de hábitos de vida saudáveis, dentre os quais a não utilização de tabaco, mesmo em formas alternativas, como por exemplo, cigarros eletrônicos, pois o uso está associado à maior predisposição às manifestações clínicas mais severas da doença.

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“…None of the hospitalized patients was a daily smoker or ex-smoker, which is consistent with several studies finding a low proportion of smokers among patients with a moderate to severe outcome. However, the relationship between smoking and COVID-19 outcome is controversial, with multiple conflicting reports in the current literature (15,20).…”

Section: Discussionmentioning

confidence: 99%

Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis

Marques¹,

Lefevre²,

Barmo³

et al. 2020

Preprint

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Objective: To investigate the prevalence, clinical features and outcomes of coronavirus disease 2019 (COVID-19) among sarcoidosis patients. Methods: We retrospectively collected features of COVID-19 in a cohort of patients with sarcoidosis followed in a single tertiary university hospital. Results: Among 199 sarcoidosis patients [mean age 58.8 (±14) years, 86 (43.2%) men], 26 (13%) were diagnosed with COVID-19 [definite (n=7), probable (n=12) and possible (n=7)]. Twenty-four out of 26 patients (92%) had at least one comorbidity, and 11/26 (42%) had two or more comorbidities. Demographic and clinical features of COVID-19 positive patients were similar to those of COVID-19 negative patients. The administration of hydroxychloroquine or immunosuppressant was not associated with the occurrence or the severity of COVID-19. Four out of 26 (15.4%) COVID-19 positive patients required admission to hospital and two of them died. Hospitalized patients [mean age of 61 (±11.5) years] were receiving higher doses of long term treatment with corticosteroids than non-hospitalized patients; 4/4 had pulmonary and 2/4 cardiac involvement of sarcoidosis, and all one or more comorbidity. Conclusion: The prevalence of COVID-19 in sarcoidosis is slightly higher to that of the general population. Almost half of the COVID-19 positive patients have two or more comorbidities and about 15% present a severe course.

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Smoking-Mediated Upregulation of the Androgen Pathway Leads to Increased SARS-CoV-2 Susceptibility

Cited by 41 publications

References 24 publications

COVID-19 and Sex Differences

COVID-19 and Sex Differences

Reflexões sobre a associação entre o tabagismo e COVID – 19: revisão de literatura

Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis

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